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Human Cytomegalovirus: CMV Infection Causes, Symptoms, Treatment
- 2. Human Cytomegalic Virus By Rani Summeya Seme Roll No. 33
- 3. Outline • Introduction • Types • Replication • Transmission • Symptoms • Complication • Pathogenesis • Immune Response • Diagnosis • Treatment • Prevention CMV
- 4. Cytomegalovirus • Greek word • Cyto= cell • Megalo= Large • Family= Herpesviridae • Natural Hosts • Human • Monkey • Enveloped virus • AKA • HCMV • Human Herpes Virus 5 • Salivary Gland Virus • Cause CMV Infection • Similar to Herpes Virus
- 5. Genome • Genome= 230kb • Linear ds DNA • Non Segmented • Monopartite • Reiterated sequence • Terminal • Internal • Split into • Unique Long • Unique Short • 150 ORF—encode protein • 41 Essential • 117 Non-Essential • For CMV Replication
- 6. Types • Acquired, or primary CMV • First-time infection • Recurring CMV • The patient is already infected • The virus is dormant and then • becomes active due to weak immune system • Congenital CMV • Occurs during pregnancy • Affects the unborn child • CMV not a problem, except • Affects an unborn child • A person with a weak immune system, • A recent transplant recipient or a • Person with HIV
- 8. Transmission • Spread by body fluids • Saliva • Blood • Urine • Vaginal fluid • Breast Milk • So possible way of transmission • Blood Transfusions • Organ Transplant • Sexual Contact • Vertical from Mother to Fetus • Direct contact • Saliva • Nasal Secretion
- 9. Symptoms • Babies with congenital CMV • Premature birth • Low Birth weight • Pneumonia • Microcephaly • Seizures • 75% babies--- Infected Brain • Patients with Weakened Immunity--- affect • Eyes • Lungs • Liver • Esophagus • Brain • Healthy people with CMV • Fatigue • Fever • Sore Throat • Muscle ache
- 10. Complication • Healthy people • Rarely cause disease • People with Weakened Immune System • CMV Mononucleosis • Too many WBCs with single nucleus • Symptoms • Sore Throat • Swollen glands • Swollen Tonsillitis • Hepatitis • Nausea • Other Complications • Gastrointestinal Problem • CNS Complications • Liver Function Problem
- 11. Pathogenesis • CMV infections--subclinical • Infects • Epithelial cells • when infected by CMV produce more virus • Macrophages • T lymphocytes. • Highly cell-associated • Causes cells to coalesce to form large cells. • Protects the virus from antibody inactivation • Suppression of cell-mediated immunity • Recurrence of symptoms • Result in severe disease • Ability to induce immunosuppression during primary infections & reactivation of latent infections • Prevents expression of MHC I --- cell surface of an infected cell. • Can also block cytokine-induced production of MHC-II on antigen presenting cells • Can also produce an IL-10 analogue that inhibits TH1 protective responses
- 12. Dissemination Tissue Tropism& Persistence • Site of inoculation • Mucosal surface • upper respiratory or genital tract. • Viremia -- mechanism for CMV dissemination to tissues in different organs • Level of viremia influenced by • CMV-encoded chemokines, chemokine receptors & cytokines • Have potential to influence by modulating cell trafficking, intracellular signaling & host cell activation • After initial infection, virus is readily isolated • urine, saliva, tears, semen, cervical secretions & human milk • Viral shedding --- 4 to 6 weeks after CMV acquisition • Viremia is often detectable at this time and can persist for months
- 13. The immune response to CMV • Toll-like Receptors (TLRs), recognize 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) • tumor necrosis factor alpha (TNF-α) • interleukin-6 (IL-6) • inflammatory cytokines recruit and activate phagocytic cells to engulf infected cells • Natural killer recruited to initial sites of infection and • eliminate HCMV-infected cells by the release of cytotoxic proteins, • which destroy target cells. • Adaptive immune response -- long-term control of HCMV • Infection results in cytotoxic CD8 T cell response • control of primary HCMV infection • reactivation from latency. • IFN-γ-secreting CD4 T cells associated with decreased virus shedding into urine • thus limiting its spread to new hosts • B cells also play a role in controlling HCMV infection
- 15. Immune evasion by HCMV • HCMV dedicates a large proportion of its genome • to down-regulating NK cell activity. • HCMV UL16 and UL142 proteins prevent the expression of NK cell • activating ligands on the surface of infected cells • HCMV UL83 can bind directly to NKp30 • prevent activation of the NK cells • US18 and US20 proteins promote the degradation of MICA • (a major stress protein) • preventing the NK cell from recognizing stress signals of an infected cell • HCMV has acquired a viral homologue of IL-10 • an immune modulatory cytokine • suppress anti-cytomegalovirus immunity. • HCMV also targets the activation of the adaptive immune response. • US11, US2 and US3 proteins down-regulate the expression of MHC class I and II molecules on cells • Virus infection of cells can trigger apoptosis of the human cell • HCMV has evolved proteins (UL36 and UL37), • which prevent apoptosis of infected cells, promoting its dissemination within the host.
- 17. Diagnosis • Most infections– undiagnosed • Little to no symptoms • Infected Individual---IgM, IgG • Blood Test • +ve --- CMV Inection • -ve --- No Infection • Patient with weakened Immune System • Regular monitoring----test for vision & Hearing • Pregnant Women • Amniocentisis • Fluid from amniotic sac • Congenital CMV suspected • Baby must be tested within 3 weeks
- 18. Treatment • No vaccine yet • Drug Therapy • CMV controlled but not cured • Drugs • Ganciclovir • Foscarnet • Delivered Intramuscularly • Acquired CMV patients---OTC painkiller • Tylenol • Ibuprofen • Aspirin • Congenital or Recurring CMV patient • Antiviral medication • Ganciclovir
- 19. Prevention • Careful hygiene--- best prevention • Clean toys and countertops • Clean any surfaces that come in contact with children's urine or saliva. • Wash the hands regularly • with soap and water. • Avoid kissing a young child • Avoid contact with • Tear • Saliva • Avoid sharing glasses and kitchen utensils • Carefully dispose of • Diapers • Paper handkerchiefs • Similar items