Вирус цитомегалии человека: причины, симптомы, диагностика и лечение вирусной инфекции

Цитомегаловирусная инфекция — симптомы, лечение, профилактика, причины, первые признаки

Общие сведения

Название вируса связано с тем, что при заражении вирусом клеток они увеличиваются в размерах (в переводе гигантские клетки).

Новости по теме

В зависимости от состояния иммунной системы заражение цитомегаловирусом может вызывать различные изменения: от бессимптомного течения и легкого мононуклеозоподобного синдрома до тяжелых системных инфекций с поражением легких, печени, почек и других органов.

Причины заболевания

Цитомегаловирус распространен повсеместно. Заражение может происходить при тесном контакте с носителем инфекции или больным. Вирус выделяется во внешнюю среду с различными биологическими жидкостями человека: слюной, мочой, калом, грудным молоком, спермой, выделениями из влагалища. К путям передачи можно отнести воздушно-капельный, пищевой, половой. Новорожденный ребенок может заразиться от матери через грудное молоко. Следует отметить вертикальный путь передачи инфекции от матери к плоду во время беременности. При заражении плода может развиваться очень тяжелое заболевание врожденная цитомегалия.

Инфицирование также может происходить при переливании крови (в России кровь доноров на наличие цитомегаловируса не проверяется) и при трансплантации органов от донора с ЦМВ-инфекцией.

Однажды заразившись цитомегаловирсом, человек как правило на всю жизнь остается носителем этой инфекции.

Симптомы ЦМВ-инфекции

Различают насколько вариантов течения ЦМВ-инфекции.

1) ЦМВ-инфекция у лиц с нормальным иммунитетом.
Чаще всего первичное инфицирование проявляется мононуклеозоподобным синдромом. Инкубационный период составляет 20-60 суток, продолжительность заболевания 2-6 недель. Как правило, отмечается лихорадка, слабость, увеличение лимфатических узлов, боли в мышцах. При достаточном иммунном ответе организм вырабатывает антитела против вируса и заболевание заканчивается самоизлечением. Выделение вирусов с биологическим жидкостями продолжается месяцы и годы после выздоровления. После первичного инфицирования цитомегаловирус может находится в организме десятки лет в неактивной форме или самопроизвольно исчезать из организма. В среднем у 90-95% взрослого населения обнаруживаются антитела класса G к ЦМВ.

2) ЦМВ-инфекция у лиц с ослабленным иммунитетом (пациенты с лимфопролиферативными заболеваниями, гемобластозами, ВИЧ-инфицированные, пациенты после трансплантации внутренних органов или костного мозга).

У таких пациентов может происходить генерализация инфекции, поражаются печень, почки, легкие, сетчатка глаза, поджелудочная железа и другие органы.

3) Врожденная цитомегаловирусная инфекция.

Внутриутробное инфицирование плода на сроке до 12 недель, как правило, заканчивается выкидышем, при заражении после 12 недель у ребенка может развиться тяжелое заболевание – врожденная цитомегалия. По статистике врожденной цитомегалией страдают примерно 5% зараженных внутриутробно новорожденных. К ее симптомам можно отнести недоношенность, увеличение печени, почек, селезенки, хориоретинит, пневмонию. У детей, перенесших внутриутробно ЦМВ-инфекцию и избежавших генерализации процесса, может выявляется задержка психомоторного развития, тугоухость, нарушения зрения, аномалии развития зубов.

Диагностика

Диагноз ЦМВ-инфекции основан на клинической картине и лабораторных методах исследования.

Лабораторные методы идентификации цитомегаловируса включают:

• выделение вируса в клеточной культуре;
• цитологическое исследование (световая микроскопия) – обнаружение специфических гигантских клеток с внутриядерным включением;
• иммуноферментный метод (ИФА) – обнаружение в крови специфических антител к цитомегаловирусу классов M и G;
• полимеразная цепная реакция – позволяет определять ДНК цитомегаловируса в любых биологических тканях.

Лечение цитомегаловируса

Вирусоносительство и мононуклеозоподобный синдром у лиц с нормальным иммунитетом лечения не требует.

Лечение назначают при выявлении различных генерализованных форм инфекции. Все применяемые противовирусные препараты (фоксарнет, ганцикловир, валганцикловир) являются токсичными и обладают массой осложнений, поэтому они назначаются только по жизненным показаниям. В некоторых случаях используют антицитомегаловирусный иммуноглобулин (цитотект). Лечение как правило проводят в условиях стационара.

Профилактика цитомегаловируса

Специальных способов профилактики ЦМВ-инфекции не разработано.

Лица со здоровым иммунитетом не нуждаются ни в лечении, ни в профилактике этого заболевания.

Лицам с ослабленным иммунитетом стараются переливать препараты крови и трансплантировать органы от ЦМВ-негативных доноров.

Основной профилактики инфицирования плода является исследование на наличие цитомегаловирусной инфекции до наступления беременности. Противовирусная терапия во время беременности не применяется, так как обладает токсичностью и имеет потенциальный риск для плода. При наличии у женщины подтвержденной лабораторными методами цитомегаловирусной инфекции беременность допустима только на фоне достижения устойчивой ремиссии.

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90000 Cytomegalovirus (CMV) infection — Symptoms and causes 90001 90002 Overview 90003 90004 Cytomegalovirus (CMV) is a common virus. Once infected, your body retains the virus for life. Most people do not know they have 90005 CMV 90006 because it rarely causes problems in healthy people. 90007 90004 If you’re pregnant or if your immune system is weakened, 90005 CMV 90006 is cause for concern. Women who develop an active 90005 CMV 90006 infection during pregnancy can pass the virus to their babies, who might then experience symptoms.For people who have weakened immune systems, especially people who have had an organ, stem cell or bone marrow transplant, 90005 CMV 90006 infection can be fatal. 90007 90004 90005 CMV 90006 spreads from person to person through body fluids, such as blood, saliva, urine, semen and breast milk. There is no cure, but there are medications that can help treat the symptoms. 90007 90020 Products & Services 90021 Show more products from Mayo Clinic 90002 Symptoms 90003 90004 Most healthy people who are infected with 90005 CMV 90006 may experience no symptoms.Some experience minor symptoms. People who are more likely to experience signs and symptoms of 90005 CMV 90006 include: 90007 90030 90031 Newborns who became infected with 90005 CMV 90006 before they were born (congenital 90005 CMV 90006). 90036 90031 Infants who become infected during birth or shortly afterward (perinatal 90005 CMV 90006). This group includes babies infected through breast milk. 90036 90031 People who have weakened immune systems, such as those who have had an organ, bone marrow or stem cell transplant, or those who are infected with HIV.90036 90043 90020 Babies 90021 90004 Most babies who have congenital 90005 CMV 90006 appear healthy at birth. 90007 90004 A few babies who have congenital 90005 CMV 90006 who appear healthy at birth develop signs over time — sometimes not for months or years after birth. The most common of these late-occurring signs are hearing loss and developmental delay. A small number of babies may also develop vision problems. 90007 90004 The following signs and symptoms are more common in babies who have congenital 90005 CMV 90006 and who are sick at birth: 90007 90030 90031 Premature birth 90036 90031 Low birth weight 90036 90031 Yellow skin and eyes (jaundice) 90036 90031 Enlarged and poorly functioning liver 90036 90031 Purple skin splotches or a rash or both 90036 90031 Abnormally small head (microencephaly) 90036 90031 Enlarged spleen 90036 90031 Pneumonia 90036 90031 Seizures 90036 90043 90020 People who have weakened immunity 90021 90004 If your immune system is weakened, you might experience serious problems that affect your: 90007 90030 90031 Eyes 90036 90031 Lungs 90036 90031 Liver 90036 90031 Esophagus 90036 90031 Stomach 90036 90031 Intestines 90036 90031 Brain 90036 90043 90020 Healthy adults 90021 90004 Most people who are infected with 90005 CMV 90006 who are otherwise healthy experience few if any symptoms.When first infected, some adults may have symptoms similar to infectious mononucleosis, including: 90007 90030 90031 Fatigue 90036 90031 Fever 90036 90031 Sore throat 90036 90031 Muscle aches 90036 90043 90020 When to see a doctor 90021 90004 See your doctor if: 90007 90030 90031 You have a weakened immune system and you’re experiencing symptoms of 90005 CMV 90006 infection. For people who have weakened immune systems, 90005 CMV 90006 infection can be serious or even fatal.People who have undergone stem cell or organ transplants seem to be at greatest risk. 90036 90031 You develop a mononucleosis-like illness while you’re pregnant. 90036 90043 90004 If you have 90005 CMV 90006 but are otherwise healthy, and you’re experiencing any mild, generalized illness, you could be in a reactivation period. Self-care, such as getting plenty of rest, should be enough for your body to control the infection. 90007 90020 When your child should see a doctor 90021 90004 If you know you were infected with 90005 CMV 90006 during your pregnancy, tell your baby’s doctor.The doctor will likely assess your baby for hearing or vision problems. 90007 90002 Causes 90003 90004 90005 CMV 90006 is related to the viruses that cause chickenpox, herpes simplex and mononucleosis. 90005 CMV 90006 may cycle through periods when it lies dormant and then reactivates. If you’re healthy, 90005 CMV 90006 mainly stays dormant. 90007 90004 When the virus is active in your body, you can pass the virus to other people.The virus is spread through body fluids — including blood, urine, saliva, breast milk, tears, semen and vaginal fluids. Casual contact does not transmit 90005 CMV 90006. 90007 90004 Ways the virus can be transmitted include: 90007 90030 90031 Touching your eyes or the inside of your nose or mouth after coming into contact with the body fluids of an infected person. 90036 90031 Sexual contact with an infected person. 90036 90031 The breast milk of an infected mother. 90036 90031 Organ, bone marrow or stem cell transplantation or blood transfusions.90036 90031 Birth. An infected mother can pass the virus to her baby before or during birth. The risk of transmitting the virus to your baby is higher if you become infected for the first time during pregnancy. 90036 90043 90002 Risk factors 90003 90004 90005 CMV 90006 is a widespread and common virus that can infect almost anyone. 90007 90002 Complications 90003 90004 Complications of 90005 CMV 90006 infection vary, depending on your overall health and when you were infected.90007 90020 Healthy adults 90021 90004 Rarely, 90005 CMV 90006 causes a healthy adult to develop mononucleosis. Other rare complications for healthy adults include problems with the digestive system, liver, brain and nervous system. 90007 90020 People who have weakened immunity 90021 90004 Complications of 90005 CMV 90006 infection can include: 90007 90030 90031 Vision loss, due to inflammation of the light-sensing layer of the eye (retinitis) 90036 90031 Digestive system problems, including inflammation of the colon (colitis), esophagus (esophagitis) and liver (hepatitis) 90036 90031 Nervous system problems, including brain inflammation (encephalitis) 90036 90031 Pneumonia 90036 90043 90020 Infants who have congenital CMV 90021 90004 An infant whose mother first became infected with 90005 CMV 90006 during pregnancy is more likely to experience complications.Complications for the baby can include: 90007 90030 90031 Hearing loss 90036 90031 Intellectual disability 90036 90031 Vision problems 90036 90031 Seizures 90036 90031 Lack of coordination 90036 90031 Weakness or problems using muscles 90036 90043 90002 Prevention 90003 90004 Careful hygiene is the best prevention against 90005 CMV 90006. You can take these precautions: 90007 90030 90031 90228 Wash your hands often.90229 Use soap and water for 15 to 20 seconds, especially if you have contact with young children or their diapers, saliva or other oral secretions. This is especially important if the children attend child care. 90036 90031 90228 Avoid contact with tears and saliva when you kiss a child. 90229 Instead of kissing a child on the lips, for instance, kiss on the forehead. This is especially important if you’re pregnant. 90036 90031 90228 Avoid sharing food or drinking out of the same glass as others.90229 Sharing glasses and kitchen utensils can spread 90005 CMV 90006. 90036 90031 90228 Be careful with disposable items. 90229 When disposing of diapers, tissues and other items that have been contaminated with bodily fluids, wash your hands thoroughly before touching your face. 90036 90031 90228 Clean toys and countertops. 90229 Clean any surfaces that come in contact with children’s urine or saliva. 90036 90031 90228 Practice safe sex. 90229 Wear a condom during sexual contact to prevent spreading 90005 CMV 90006 through semen and vaginal fluids.90036 90043 90004 If you have weakened immunity, you may benefit from taking antiviral medication to prevent 90005 CMV 90006 disease. 90007 90004 Experimental vaccines are being tested for women of childbearing age. These vaccines may be useful in preventing 90005 CMV 90006 infection in mothers and infants, and reducing the chance that babies born to women who are infected while pregnant will develop disabilities. 90007 90264 .90000 Cytomegalovirus: Symptoms, treatments, and types 90001 90002 Cytomegalovirus is a common herpes virus. Many people do not know they have it, because they may have no symptoms. 90003 90002 But the virus, which remains dormant in the body, can cause complications during pregnancy and for people with a weakened immune system. 90003 90002 The virus spreads through bodily fluids, and it can be passed on from a pregnant mother to her unborn baby. 90003 90002 Also known as HCMV, CMV, or Human Herpes virus 5 (HHV-5), cytomegalovirus is the virus most commonly transmitted to a developing fetus.90003 90002 The Centers for Disease Control and Prevention (CDC) estimates that over 50 percent of adults in the United States are infected by the age of 40 years. It affects males and females equally, at any age, and regardless of ethnicity. 90003 90002 The symptoms will depend on the type of CMV. 90003 90002 90015 Acquired CMV 90016 90003 90002 Most people with acquired CMV have no noticeable symptoms, but if symptoms do occur, they may include: 90003 90002 Symptoms will generally go away after two weeks.90003 90002 90015 Recurring CMV 90016 90003 90002 Symptoms of recurring CMV vary, depending on which organs are affected. Areas likely to be affected are the eyes, lungs, or digestive system. 90003 90002 Symptoms may include: 90003 90030 90031 fever 90032 90031 diarrhea, gastrointestinal ulcerations, and gastrointestinal bleeding 90032 90031 shortness of breath 90032 90031 pneumonia with hypoxemia, or low blood oxygen 90032 90031 mouth ulcers that can be large 90032 90031 problems with vision, including floaters, blind spots, and blurred vision 90032 90031 hepatitis, or inflamed liver, with prolonged fever 90032 90031 encephalitis, or inflammation of the brain, leading to behavioral changes, seizures, and even coma.90032 90047 90002 A person with a weakened immune system who experiences any of these symptoms should seek medical attention. 90003 90002 90015 Congenital CMV 90016 90003 90002 Around 90 percent of babies born with CMV have no symptoms, but 10 percent to 15 percent of them will develop hearing loss, normally during their first 6 months of life. The severity ranges from slight to total hearing loss. 90003 90002 In half of these children, just one ear will be affected, but the rest will have hearing loss in both ears.Hearing loss in both ears can lead to a higher risk of speech and communication problems later on. 90003 90002 If there are symptoms of congenital CMV at birth, they may include: 90003 90030 90031 jaundice 90032 90031 pneumonia 90032 90031 red spots under the skin 90032 90031 Purple skin splotches, a rash, or both 90032 90031 enlarged liver 90032 90031 enlarged spleen 90032 90031 low birth weight 90032 90031 seizures 90032 90047 90002 Some of these symptoms are treatable. 90003 90002 In about 75 percent of babies born with congenital CMV, there will be an impact on the brain.This may lead to challenges later in life. 90003 90002 Conditions that they may face include: 90003 90030 90031 autism 90032 90031 central vision loss, scarring of the retina, and uveitis, or swelling and irritation of the eye 90032 90031 cognitive and learning difficulties 90032 90031 deafness or partial hearing loss 90032 90031 epilepsy 90032 90031 impaired vision 90032 90031 problems with physical coordination 90032 90031 seizures 90032 90031 small head 90032 90047 90002 Scientists have been searching for a CMV vaccine, but as yet there is no cure.90003 90002 People with acquired CMV, who are infected for the first time, can use over-the-counter (OTC) painkillers such as Tylenol (acetaminophen), ibuprofen, or aspirin to relieve symptoms, and should drink plenty of fluids. 90003 90002 Patients with congenital or recurring CMV can use anti-viral medications such as ganciclovir to slow the spread of the virus. 90003 90002 These medications may have adverse effects. If there is extensive organ damage, hospitalization may be necessary.90003 90002 Newborns may need to stay in the hospital until their organ functions return to normal. 90003 90114 Prevention 90115 90002 The following precautions may help lower the risk of contracting CMV: 90003 90030 90031 Wash the hands regularly with soap and water. 90032 90031 Avoid kissing a young child, including tear and saliva contact. 90032 90031 Avoid sharing glasses and kitchen utensils, for example, passing round a drink. 90032 90031 Dispose of diapers, paper handkerchiefs, and similar items carefully.90032 90031 Use a condom to prevent the spread of CMV via vaginal fluids and semen. 90032 90047 90002 The CDC urges parents and caregivers of children with CMV to seek treatment as early as possible, whether it is medication or attending services such as hearing checks. 90003 90002 There are three main types of CMV infections: acquired, recurring, or congenital. 90003 90030 90031 Acquired, or primary, CMV is a first-time infection. 90032 90031 Recurring CMV is when the patient is already infected.The virus is dormant and then becomes active due to a weak immune system. 90032 90031 Congenital CMV is when infection occurs during pregnancy and affects the unborn child. 90032 90047 90002 CMV is generally not a problem, except when it affects an unborn child or a person with a weak immune system, such as a recent transplant recipient or a person with human immunodeficiency virus, or HIV. 90003 90002 In people with HIV, CMV infection can lead to organ failure, eye damage, and blindness.Improvement in antiviral medication has reduced the risk in recent years. 90003 90002 Organ and bone marrow transplant recipients have to take immunosuppressants to lower their immune systems, so that their bodies do not reject the new organs. Dormant CMV can become active in these patients and lead to organ damage. 90003 90002 Transplant recipients may receive antiviral medicines as a precaution against CMV. 90003 90002 During pregnancy, CMV infection can pass from the mother to the fetus.This is called congenital CMV. 90003 90002 According to the CDC, around 1 in 150 newborns are already infected with CMV at birth. 90003 90002 Most of these infants will have no signs or symptoms, but around 20 percent of them will have symptoms or long-term health complications, including learning difficulties. 90003 90002 The symptoms may be severe, and they include vision and hearing loss, vision loss, small head size, weakness and difficulty using muscles, problems of coordination, and seizures.90003 Share on PinterestCytomegalovirus is a common herpes virus that affects 50 percent of people by the age of 40 years. 90002 Acquired cytomegalovirus can spread between people through bodily fluids, such as saliva, semen, blood, urine, vaginal fluids, and breast milk. 90003 90002 Infection may also occur by touching a surface infected with saliva or urine, and then touching the inside of the nose or mouth. 90003 90002 Most humans become infected during childhood, at daycare centers, nurseries, and places where children are in close contact with each other.However, by this age, the child’s immune system is normally able to deal with an infection. 90003 90002 Recurring CMV can occur in patients with a weakened immune system due to HIV, organ transplantation, chemotherapy or taking oral steroids for over 3 months. 90003 90002 Congenital CMV normally occurs when a woman is infected with CMV for the first time, either during her pregnancy or shortly before conceiving. 90003 90002 Occasionally, a dormant CMV infection may recur during pregnancy, especially if the mother has a weakened immune system.90003 90002 A blood test can detect the antibodies which are created when the immune system responds to the presence of CMV. 90003 90002 A pregnant woman has a very small risk of reactivation infecting her developing baby. If infection is suspected, she may consider amniocentesis, which involves extracting a sample of amniotic fluid to find out whether the virus is present. 90003 90002 If congenital CMV is suspected, the baby must be tested within the first 3 weeks of life. Testing later than 3 weeks will not be conclusive for congenital CMV, because the infection could have happened after birth.90003 90002 Any patient with a weakened immune system should be tested, even if there is no active CMV infection. Regular monitoring for CMV complications will include testing for vision and hearing problems. 90003 90002 Healthy people very rarely become significantly sick from CMV infection. 90003 90002 People with a weakened immune system, however, may develop CMV mononucleosis, a condition in which there are too many white blood cells with a single nucleus. Symptoms include sore throat, swollen glands, swollen tonsils, tiredness, and nausea.It can cause liver inflammation, or hepatitis, and spleen enlargement. 90003 90002 CMV mononucleosis is similar to classic mononucleosis, caused by the Epstein-Barr Virus. EBV mononucleosis is also known as glandular fever. 90003 90002 Other complications of CMV are: 90003 90030 90031 gastrointestinal problems, including diarrhea, fever, abdominal pain, colon inflammation, and blood the in feces 90032 90031 liver function problems 90032 90031 central nervous system (CNS) complications, such as encephalitis, or inflammation of the brain 90032 90031 pneumonitis, or inflammation of lung tissue.90032 90047.90000 Human Cytomegalovirus (HCMV) | British Society for Immunology 90001 90002 HCMV-associated disease 90003 90004 Human cytomegalovirus (HCMV) is a beta-herpesvirus that causes lifelong infection in humans. HCMV has a prevalence of 55-100% within the human population, depending on different socioeconomic and geographical factors. Primary HCMV infection is generally asymptomatic in healthy hosts but can cause severe and sometimes fatal disease in immunocompromised individuals and neonates.HCMV is the leading infectious cause of congenital abnormalities in the Wwestern world, affecting 1-2.5% of 90005 90004 all live births. HCMV intrauterine infection and can cause significant morbidity, including low birth weight, hearing loss, visual impairment, microcephaly, hepatosplenomegaly, and varying degrees of mental retardation. 90005 90004 HCMV also causes serious disease in organ transplant recipients and AIDS patients, either after primary infection or reactivation of latent infection.In immunocompromised individuals, HCMV infection is often controlled by early treatment with antivirals but problems exist such as toxicity, the emergence of antiviral-resistant HCMV strains and the availability of antiviral drugs in developing countries. 90005 90002 The immune response to cytomegalovirus 90003 90004 Extracellular and intracellular pathogen recognition receptors, such as Toll-like Receptors (TLRs), recognise components of the virion, which triggers the innate immune response to the virus.This leads to the production of inflammatory cytokines, such as type 1 interferons (IFN), tumour necrosis factor alpha (TNF-α) and interleukin-6 (IL-6). These inflammatory cytokines can recruit and activate phagocytic cells, such as dendritic cells, which can engulf HCMV-infected cells. Natural killer (NK) cells are also recruited to initial sites of infection and eliminate HCMV-infected cells by the release of cytotoxic proteins, which destroy target cells. Furthermore, data from the murine cytomegalovirus (MCMV) model of infection suggests that neutrophils contribute to early control of virus infection.90005 90004 The adaptive immune response contributes to the long-term control of HCMV. HCMV infection results in an extremely large cytotoxic CD8 T cell response that appears to be crucial for the control of primary HCMV infection and reactivation from latency. Also, HCMV-specific IFN-γ-secreting CD4 T cells are associated with decreased virus shedding into urine, thus limiting its spread to new hosts. B cells also play a role in controlling HCMV infection and may also help prevent its transmission to new hosts as maternal antibodies can confer protection to foetuses in utero.90005 90004 A summary of the immune responses to HCMV is shown in Figure 1 90005 90018 90004 90020 Figure 1: Summary of immune responses to CMV infection 90021 90005 90002 Immune evasion by HCMV 90003 90004 HCMV has co-evolved with humans for millions of years. During this time, it has acquired a number of different mechanisms that modulate and evade the human immune response, which allows for more efficient infection and dissemination within the body. HCMV dedicates a large proportion of its genome to down-regulating NK cell activity.The HCMV UL16 and UL142 proteins prevent the expression of NK cell activating ligands on the surface of infected cells, while the HCMV UL83 can bind directly to NKp30, an activating NK cell receptor, and prevent activation of the NK cells. Furthermore, the HCMV US18 and US20 proteins promote the degradation of MICA (a major stress protein), preventing the NK cell from recognising stress signals of an infected cell. HCMV has acquired a viral homologue of IL-10, an immune modulatory cytokine that has been demonstrated to suppress anti-cytomegalovirus immunity.HCMV also targets the activation of the adaptive immune response. The HCMV US11, US2 and US3 proteins down-regulate the expression of major histocompatibility complex (MHC) class I and II molecules on cells, such as antigen presenting cells, which prevents the presentation of HCMV-derived peptides bound to MHC molecules to unstimulated T cells, a process required for the activation of T cells. 90005 90004 Virus infection of cells can trigger apoptosis of the human cell, a programmed cell death mechanism that is important for limiting the spread of the virus.These apoptotic cells are then cleared by phagocytic cells, thus preventing the release of new virions. However, HCMV has evolved proteins (UL36 and UL37), which prevent apoptosis of infected cells, promoting its dissemination within the host. A summary of immune evasion mechanism employed by HCMV is outlined in Figure 2. 90005 90029 90004 90020 Figure 2: Summary of immune evasion mechanisms by HCMV 90021 90005 90004 Despite the plethora of immune evasion mechanisms developed by HCMV, the human immune system still produces a robust immune response in response to this virus.This is clearly demonstrated by the fact that most primary infections in immunocompetent hosts are asymptomatic and that HCMV disease occurs mainly in those with compromised or immature immune systems. Current research aims to fully elucidateing the mechanisms by which HCMV manipulates the human immune system in order to improve antiviral therapies and to develop a vaccine capable of boosting the initial antiviral immune response, thus preventing the establishment of HCMV infection. 90005 90004 Human Cytomegalovirus | Bite-Sized Immunology © The copyright for this work resides with the author 90005 .90000 Human Cytomegalovirus | Virology | Microbe Notes 90001 90002 Home »Virology» 90003 Human Cytomegalovirus 90004 90005 90002 Last Updated on: 90007 January 17, 2020 90008 by Sagar Aryal 90005 90010 90011 Structure of 90004 Human Cytomegalovirus 90013 90002 90015 90005 90002 90011 Figure: Structure of Human Cytomegalo Virus, Source: Dr. Marko Reschke, Marburg, Germany 90004 90005 90021 90022 Cytomegalovirus is a member of the herpes virus family that falls under the beta herpes subfamily.90023 90022 CMV is spherical in shape with icosahedral symmetry. 90023 90022 The icosahedral protein capsid with an average diameter of 100 nm consists of 162 hollow hexagonal and pentagonal capsomeres with an electron-dense core containing the double-stranded DNA genome with 230 kbp nucleotides together forming the nucleocapsid. 90023 90022 The nucleocapsid is surrounded by an envelope which is lipoprotein in nature. 90023 90022 The lipid part is derived from the nuclear membrane of the infected host cell.90023 90022 Projecting from the trilaminar lipid host-derived envelope are spikes of viral glycoproteins which bind to specific host receptor and mediate virus entry. 90023 90022 gB is one of the major surface glycoproteins in CMV which influences virus binding to and entry into the cell and cell to cell transmission. 90023 90022 gH is a second relatively abundant glycoprotein which is a target for complement independent neutralizing antibodies. 90023 90022 In mature virus particles, outside the capsid is an amorphous proteinaceous layer, the tegument, surrounded by a lipid envelope derived from host cell membranes.90023 90022 At least 25 proteins are located in the tegument layer. 90023 90022 The tegument consists of enzymes such as VP16 which is responsible for subverting cellular proteins and enzymes to involve in viral nucleic acid replication and VHS (Virion Host Shutoff) protein which shut off the host cell protein synthesis in the cytoplasm. 90023 90044 90010 90011 Genome of Human Cytomegalovirus 90004 90013 90002 90050 90005 90002 90011 Figure: Genome of Human Cytomegalo Virus, Source: https: // doi.org / 10.3390 / v4112448 90004 90005 90021 90022 The CMV genome consists of approximately 230kb of linear double-stranded DNA. 90023 90022 The genome is monopartite and contains terminal and internal reiterated sequences. 90023 90022 The genome is split into a unique long (UL) and a unique short (US) region, both flanked by inverted sequences. 90023 90022 It contains approximately 150 open reading frames (ORFs) that encode proteins. 90023 90022 Out of these, it has been found that 41 are essential and 117 are nonessential for CMV replication.90023 90044 90010 90011 Transmission and Epidemiology 90004 90013 90021 90022 CMV infections occur worldwide and the prevalence of infection varies considerably. 90023 90022 CMV is transmitted across the placenta within the birth canal and quite commonly in breast milk, in young children commonly through saliva. 90023 90022 It can also be transmitted sexually showing presence in both semen and cervical secretions. 90023 90022 Furthermore, it can also be transmitted via blood transfusion and during organ transplantation.90023 90022 Congenital CMV infection is the most common viral infection of human fetuses with 1% in the USA and 2-3% in developing countries. 90023 90044 90010 90011 Replication of Human Cytomegalovirus 90004 90013 90088 90022 Attachment to host cells is mediated by the fusion of the viral glycoproteins to host receptors which further mediates endocytosis of the virus into the host cell. 90023 90022 After entry and uncoating, the capsid is transported to the nuclear pore where the viral DNA is released into the nucleus.90023 90022 Tegument proteins regulate host cell responses and initiate the temporal cascade of the expression of viral I immediate-early (IE) genes, followed by delayed early (DE) genes, which initiate viral genome replication, and late (L) genes. 90023 90022 Late gene expression initiates capsid assembly in the nucleus, followed by nuclear egress to the cytosol. 90023 90022 Capsids associate with tegument proteins in the cytosol and are trafficked to the viral assembly complex (AC) that contains components of the endoplasmic reticulum (ER), Golgi apparatus and endosomal machinery.90023 90022 The capsids further acquire tegument and viral envelope by budding into intracellular vesicles at the assembly complex. 90023 90022 Assembly of the virus in nuclear viral factories and budding through the inner lamella of the nuclear membrane by the insertion of herpes glycoproteins, throughout the Golgi and final release by exocytosis at the plasma membrane. 90023 90103 90010 90105 90013 90002 Image Source: MDPI Viruses 90005 90010 90011 Pathogenesis of Human Cytomegalovirus 90004 90013 90021 90022 HCMV infects and replicates in a wide variety of cells, including epithelial cells of the gland and mucosal tissue, smooth muscle cells, fibroblasts, macrophages, dendritic cells, hepatocytes, and vascular endothelial cells.90023 90022 This broad cell tropism facilitates systemic spread in the human body and inter-host spread. 90023 90022 Primary replication typically starts with replication in the mucosal epithelium as a result of direct contact with infectious secretions from an infected individual. 90023 90022 A systemic phase of infection disseminates virus in the host via leukocyte associated viremia that may last for several months. 90023 90022 In addition, HCMV undergoes latency in myeloid cells of the bone marrow, presumably leading to a life-long infection with sporadic reactivation.90023 90022 HCMV infection is generally asymptomatic in healthy individuals. However, in immunocompromised individuals, such as organ transplant recipients or human immunodeficiency virus carriers, HCMV poses a life-threatening risk. 90023 90022 HCMV is also recognized as the leading infectious cause of congenital neurological disease by transmission through the placenta from the mother to the child. 90023 90022 CMV specific IgM antibodies are produced during the primary infection and persist for 3 or 4 months, but are not produced in recurrent infections in immunocompetent individuals.90023 90022 CMV IgG antibodies are produced at the time of primary infection and persist lifelong. 90023 90022 With intrauterine infections, both IgM and IgG are produced by the fetus but the fetal IgG response can only be detected as the passively acquired IgG from the mother is catabolized. 90023 90022 On the other hand, Cell-mediated immunity (CMI) is thought to play a key role in the suppression of CMI infection. 90023 90044 90010 90011 Clinical manifestations of Human Cytomegalovirus 90004 90013 90021 90022 Acute CMV infection may mimic infectious mononucleosis caused by Epstein-Barr virus or liver infection by hepatitis A, B, or C.90023 90022 Mono-like symptoms may include fever, malaise, enlarged lymph nodes, sore throat, muscle aches, loss of appetite, enlarged liver or spleen, and fatigue. 90023 90022 Hepatitis-like symptoms and signs may include appetite loss, yellow eyes, nausea, and diarrhea. 90023 90022 In people with suppressed immune systems, CMV infection can attack different organs of the body and may cause blurred vision and blindness (CMV retinitis), lung infection (pneumonia), painful swallowing (esophagitis), diarrhea (colitis), inflammation of the liver (hepatitis), or inflammation of the brain (encephalitis), which may cause behavioral changes, seizures, or coma.90023 90022 Infants with CMV infection at birth (congenital CMV) have no symptoms at birth, however, up to 20% of those without symptoms at birth will go on to develop deafness. 90023 90022 Only about 10% of infants with congenital CMV show signs and symptoms of the infection or develop complications. 90023 90022 Signs and symptoms of CMV at birth may include deafness, yellow skin, and eyes (jaundice), skin rash, premature birth, low birth weight, pneumonia, enlarged liver and spleen, microcephaly, or seizures.90023 90022 The effects of congenital CMV infection include: 90021 90022 CNS abnormalities — microcephaly, mental retardation, spasticity, epilepsy, periventricular calcification 90023 90022 choroidoretinitis and optic atrophy 90023 90022 sensorineural deafness 90023 90022 hepatosplenomegaly and jaundice which is due to hepatitis 90023 90022 pneumonitis 90023 90022 myocarditis 90023 90022 Thrombocytopenic purpura 90023 90022 Hemolytic anemia 90023 90022 Late sequelae — damage to the enamel forming organ of the teeth resulting in yellow discoloration of the teeth and brittleness.90023 90044 90023 90044 90010 90011 Laboratory diagnosis of Human Cytomegalovirus 90004 90013 90002 90011 Specimen: 90004 urine, saline, tissue biopsy and other body fluids 90005 90088 90022 90011 Virus isolation 90004 90023 90103 90021 90022 Human embryo lung fibroblasts are most commonly used. 90023 90022 The specimen is inoculated into HEL cells and kept for 28 days with a blind passage at 14 days. 90023 90022 CMV produces a typical focal cytopathic effect. 90023 90044 90201 90022 90011 Microscopy 90004 90023 90103 90021 90022 Virions in the urine of congenitally infected infants may be visualized by EM 90023 90044 90211 90022 90011 Cytopathology 90004 90023 90103 90021 90022 Intracellular inclusions surrounded by a clear halo may be demonstrated with various stains (Giemsa, Wright, hematoxylin-eosin, Papanicolaou).90023 90022 Cytomegalic inclusions can be recognized from biopsy material by the typical «owl’s eyes appearance». 90023 90044 90223 90022 90011 Tissue immunofluorescence 90004 90023 90103 90021 90022 Infected lung and liver cells may be stained by specific anti-CMV antibodies. 90023 90044 90233 90022 90011 Immunohistochemistry 90004 90023 90103 90021 90022 Immunohistochemistry is performed primarily on tissue or body fluid samples. 90023 90022 Slides are made from frozen sections of biopsy tissue samples (liver, lung) or by centrifuging cells onto a slide.90023 90022 Then monoclonal or polyclonal antibodies against early CMV antigens are applied and visualized by fluorescently labeled antibodies or enzyme-labeled secondary antibodies which are visualized by the change of color of the substrate. 90023 90022 The stained slides are then examined by fluorescent or light microscopy. 90023 90044 90249 90022 90011 Antigen detection 90004 90023 90103 90021 90022 Antigenemia is defined as the detection of the CMV pp65 antigen in leukocytes.90023 90022 The pp65 assay is used to detect messenger matrix proteins on the CMV virus, with either immunofluorescence assay or messenger RNA amplification 90023 90044 90261 90022 90011 Serology 90004 90023 90103 90021 90022 Serological tests are useful for determining whether a patient has had CMV infection in the past, determined by the presence or absence of CMV IgG. 90023 90022 The methods used for detection include complement fixation, enzyme-linked immunosorbent assay (ELISA), anti-complement immunofluorescence, radioimmunoassay, and indirect hemagglutination.90023 90022 The detection of IgM antibodies has been used as an indicator of acute or recent infection. 90023 90022 The IgM capture assays are widely employed and are based on selective binding of IgM antibody to the solid phase. 90023 90044 90277 90022 90011 Molecular methods 90004 90023 90103 90021 90022 Polymerase chain reaction (PCR) is a widely available rapid and sensitive method of CMV detection based on the amplification of nucleic acids. 90023 90022 PCR for CMV DNA can be either qualitative or quantitative, in which the amount of viral DNA in the respective sample is measured.90023 90022 The quantitative PCR (Real-Time PCR) allows for continuous monitoring of immunocompromised individuals to identify patients at risk for CMV disease for preemptive therapy and to determine response to treatment. 90023 90022 Nucleic acid sequence-based amplification (NASBA) assay allows the specific nucleic assay sequence-based amplification of unspliced ​​viral mRNAs (late pp67 mRNA expression) in a background of DNA using a specific isothermal technique of amplification. 90023 90044 90010 90011 Treatment 90004 90013 90021 90022 The drugs ganciclovir and foscarnet have been licensed for use in life-threatening CMV infection in immunocompromised patients.90023 90022 Ganciclovir remains the mainstay of treatment in severe CMV disease other than retinitis. 90023 90022 Foscarnet and cidofovir are used as second-line drugs. 90023 90022 Acyclovir and valacyclovir have shown some benefits in the bone marrow and renal transplant patients. 90023 90044 90010 90011 Prevention and control 90004 90013 90021 90022 Isolation of newborns with generalized cytomegalic inclusion disease from other newborns is advisable. 90023 90022 Screening of transplant donors and recipients for CMV antibody.90023 90022 Administration of human IgG prepared from plasma pools has given discordant results in tests to decrease the incidence of viral infections in transplant recipients. 90023 90022 Both live and recombinant vaccines are under development. 90023 90044 90002 90011 Sources 90004 90005 90021 90022 6% — https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3730495/ 90023 90022 6% — https://www.medicinenet.com/cytomegalovirus_cmv/article.htm 90023 90022 3% — https://www.slideshare.net/abdullahabobakr7/cytomegalovirus-27430084 90023 90022 3% — https: // www.ncbi.nlm.nih.gov/pmc/articles/PMC4604749/ 90023 90022 2% — https://www.sciencedirect.com/topics/biochemistry-genetics-and-molecular-biology/herpesviridae 90023 90022 2% — https://www.ijcmas.com/vol-4-11/M.%20Ram%20Mohan%20Rao%20and%20Syam%20D%20Gopal.pdf 90023 90022 2% — https://emedicine.medscape.com/article/215702-workup 90023 90022 2% — http://www.virology-online.com/viruses/CMV2.htm 90023 90022 2% — http://virology-online.com/viruses/CMV.htm 90023 90022 1% — https://www.youtube.com/watch?v=K-fdNrfbhUM 90023 90022 1% — https: // www.virology-online.com/viruses/CMV.htm 90023 90022 1% — https://www.sciencedirect.com/science/article/pii/016609349090077S 90023 90022 1% — https://www.researchgate.net/publication/12293630_Viral_entry_into_the_nucleus 90023 90022 1% — https://www.pnas.org/content/pnas/100/24/14223.full.pdf 90023 90022 1% — https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4385066/ 90023 90022 1% — https://viralzone.expasy.org/complete_by_species/18.html 90023 90022 1% — https://viralzone.expasy.org/by_species/180 90023 90022 1% — https: // quizlet.com / 30877982 / micro-mini-6-flash-cards / 90023 90022 1% — https://quizlet.com/207698031/chapter-9-bio-02-flash-cards/ 90023 90022 1% — https://academic.oup.com/tropej/article/61/2/79/1728980 90023 90022 1% — http://www.signavitae.com/2015/06/congenital-cytomegalovirus-infection-case-report/ 90023 90022 <1% - https://www.sciencedirect.com/topics/chemistry/double-stranded-dna 90023 90022 <1% - https://www.researchgate.net/publication/51046937_Cytomegalovirus_CMV 90023 90022 <1% - https: // www.researchgate.net/publication/265514663_The_pathogenesis_of_human_cytomegalovirus 90023 90022 <1% - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3144558/ 90023 90022 <1% - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2885759/ 90023 90022 <1% - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2415745/ 90023 90022 <1% - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1563938/ 90023 90022 <1% - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC112471/ 90023 90022 <1% - https: //www.nature.com / articles / 6364293 90023 90022 <1% - https://www.medscape.com/answers/215702-99981/which-medications-are-used-in-the-management-of-cytomegalovirus-cmv-disease 90023 90022 <1% - https://www.mdpi.com/1422-0067/20/15/3626/pdf-vor 90023 90022 <1% - https://www.klinikum.uni-heidelberg.de/zentrum-fuer-infektiologie/virologie/forschung/forschungsgruppen/kraeusslich/ 90023 90022 <1% - https://quizlet.com/49419439/chapter-6-flash-cards/ 90023 90022 <1% - https://labtestsonline.org/articles/anatomic-pathology 90023 90022 <1% - https: // laboratoryinfo.com / elisa / 90023 90022 <1% - https://ijponline.biomedcentral.com/articles/10.1186/s13052-017-0358-8 90023 90022 <1% - https://aem.asm.org/content/71/11/7113 90023 90022 <1% - http://www.plantcell.org/content/11/4/643 90023 90022 <1% - http://www.authorstream.com/Presentation/doctorrao-2175697-cytomegalovirus/ 90023 90022 <1% - http://onlinelibrary.wiley.com/doi/10.1111/j.1651-2227.1962.tb08674.x/abstract 90023 90022 <1% - http://europepmc.org/articles/PMC138598 90023 90044 90010 90011 90413 Human Cytomegalovirus 90414 90004 90013 90417 Categories Virology Tags CMV, Cytomegalovirus, Human Cytomegalovirus, Virology, Virus Post navigation .