--- MEDICAL VIROLOGY & MYCOLOGY MOUNT KENYA UNIVERSITY — MBCHB YEAR 3 UNIT CODE: MBMM 3300 / MBMM 3333 TARGETED EXAM NOTES — SECTION 1 OF 3 Based on past papers
--- MEDICAL VIROLOGY & MYCOLOGY MOUNT KENYA UNIVERSITY — MBCHB YEAR 3 UNIT CODE: MBMM 3300 / MBMM 3333 TARGETED EXAM NOTES — SECTION 1 OF 3 Based on past papers: 2017/2018, 2018/2019, 2021/2022 and CAT papers. Asterisk = must know, appears in essays and/or repeatedly across papers. --- 1. VIRAL PATHOGENESIS Correct order of stages — tested in EVERY paper:- Viral entry at skin or mucosal surface - Primary replication - Viremia - Replication within target organs - - Resistance to viral infection LEAST likely depends on: size of viral genome and gender of exposed individual. It DOES depend on immunocompetence, history of immunization, and age. Persistent infections: viruses causing them have evolved mechanisms to escape detection and/or clearance by the host immune system. They do NOT require defective immunity to establish persistence. --- 2. VIRUS AND RESPIRATORY TRACTFactors important in virus-respiratory tract interaction:- Mucociliary transport - Size of aerosolized droplets - Relatively low temperature of upper airways - Mucosal IgA production - - NOT important: M cells — this is the MCQ trick answer used repeatedly. Early host defense (LEAST important in early infection): virus-specific cytotoxic lymphocytes. These are a late response. Early defenses are mucociliary transport, macrophages, interferons alpha and beta, natural killer cells. --- 3. HERPES SIMPLEX VIRUS (HSV) Tested in every single paper. High priority for essays and MCQs.Types that cause genital herpes: HSV-1 and HSV-2 only. Not HPV, not HTLV1, not HIV. Portal of entry: mucous membranes and skin. Target cells: mucous membranes and neurons. HSV establishes latency in neurons and travels to CNS along nerve fibers — this is how it bypasses the blood-brain barrier. Pathogenesis must knows: - Most HSV-2 seropositive persons report NO symptoms but still shed virus intermittently from genital area - Primary first episode: lesions present, symptoms usually severe, NEITHER HSV-1 nor HSV-2 antibodies are present yet - HSV-2 IS associated with HIV acquisition and transmission - Patient with HSV is ALWAYS at risk for shedding the virus — this answer appears in essays and MCQs - - Herpesvirus family — incorrect statement to identify in MCQ: they replicate in host cell NUCLEUS, not cytoplasm. Everything else about them is true — they are enveloped, latent, cause recurrent infections, common in immunocompromised. Treatment — systemic antiviral chemotherapy: - Acyclovir - Valacyclovir - Famciclovir - - All three are correct. This comes up repeatedly. Transmission facts: - HSV is readily inactivated by drying and soap and water - Average incubation period is NOT 10 days — this is the trick option - Likelihood of transmission does NOT decrease with increased duration of infection - - --- 4. VARICELLA-ZOSTER VIRUS (VZV)Portal of entry: respiratory epithelium Most contagious period: 1-2 days PRIOR to development of the rash --- 5. CYTOMEGALOVIRUS (CMV)Essay question in 2018/2019 and 2021/2022 — very high priority.Group most likely to develop virulent CMV infection: newborns Congenital CMV infection causes: - Mental retardation - Enlarged spleen - Liver damage - Petechial rash, low birth weight, hepatosplenomegaly, bilateral cataracts - - All of the above can occur. Any of these answers is correct. Pathogenesis of CMV: - Primary infection often asymptomatic in immunocompetent - CMV establishes latency in mononuclear cells - Reactivates in immunocompromised — transplant patients, HIV patients, newborns - Diagnosis: detection of CMV pp65 antigen, PCR, shell vial culture - - Prevention and diagnosis: - Preventive measures: antiviral prophylaxis in transplant patients (ganciclovir), screening of blood products, avoid exposure in pregnancy - Diagnosis: serology, PCR, culture, antigenemia assay - - --- 6. EPSTEIN-BARR VIRUS (EBV)Associated with: Burkitt lymphoma AND infectious mononucleosis — both caused by EBV. This is a repeated MCQ.Niche in humans: lymphoid tissue and salivary glands Also associated with nasopharyngeal carcinoma — but note: EBV causing nasopharyngeal carcinoma is TRUE, not false. Know this distinction for the except questions. --- 7. HEPATITIS VIRUSES Tested in every paper.Hepatitis A: - Transmission: fecal-oral route — always the answer - Diagnosis: detection of IgM anti-HAV by ELISA — most reliable method - Initial site of replication: GIT - Diagnosis is NOT made by isolating virus in cell culture - Member of Picornaviridae family - Immunoglobulin used to prevent disease in exposed persons - - Hepatitis B: - Only DNA virus that causes hepatitis — comes up in every paper - Found in: blood, semen, AND saliva — all of these - Transmitted parenterally, sexually, mother to child - - Hepatitis C: RNA virus Hepatitis D: RNA virus, requires HBV co-infection Hepatitis E: RNA virus, fecal-oral like HAV --- 8. INFLUENZA VIRUSEssay and MCQ — antigenic changes are very heavily tested.Antigenic drift: minor change, gradual, point mutation affecting major antigenic sites on surface glycoprotein Antigenic shift: major change, abrupt change due to genetic reassortment with unrelated strains, results in emergence of a new subtype — this is what causes pandemics What increases possibility of antigenic shift: simultaneous infection of one individual with two different strains of influenza Haemagglutinin (HA) and Neuraminidase (NA): glycoproteins on influenza virus that contribute to virulence. HA = binding/attachment. NA = transmission, cleaves sialic acid aiding release of virus. NOT TRUE about Influenza A — repeated MCQ trick: vaccination confers lifelong protection. This is FALSE. Everything else — may undergo antigenic shift and drift, may cause pandemics, responds to rimantidine, responds to neuraminidase inhibitors — all TRUE. Paramyxovirus that causes mumps targets: parotid gland Member of paramyxovirus family that causes serious croup: Respiratory syncytial virus (RSV) --- 9. POLIOVIRUSAffinity for: nervous system — not GIT, not circulatory systemSurvives gastric environment because: it has a naked capsid — no envelope to be destroyed by acid Transmitted: alimentary (fecal-oral) route --- 10. RABIES VIRUS Pathogenesis — essay question in CAT 2018/2019:- Virus enters through bite of infected wild animal - Grows at trauma site for weeks, multiplies in muscle - Travels to spinal cord and CNS through nerve cells - Intensive multiplication in CNS - Migrates to salivary glands causing excessive drooling - - Post-exposure treatment: - Passive: Human Rabies Immune Globulin (HRIG) - Active: Human Diploid Cell Vaccine (HDCV) - - --- 11. RETROVIRUSES AND HIVEssay in 2021/2022 — reverse transcriptase and integrase — high priority.Retroviruses: contain two complete copies of positive strand RNA and the enzyme reverse transcriptase The positive strand does NOT act as messenger but becomes converted into DNA and integrated into host cellular DNA Reverse transcriptase role in HIV: - Converts viral RNA into DNA (reverse transcription) - Essential for viral replication - Target for antiretroviral drugs — NRTIs and NNRTIs - - Integrase role in HIV: - Integrates viral DNA into host cell genome - Target for integrase inhibitors (e.g. raltegravir) - - Selectively toxic antiretrovirals: drugs that target viral enzymes (reverse transcriptase, integrase, protease) are selectively toxic because these enzymes are specific to the virus and have no equivalent in human cells Classes of drugs used in HIV/AIDS therapy: - Synthetic nucleotides - Reverse transcriptase inhibitors - Protease inhibitors - Fusion inhibitors - NOT ribozyme inhibitors — this is the trick MCQ answer - - Mode of HIV transmission growing most rapidly: sharing of contaminated needles --- 12. ARBOVIRUSESNucleocapsid: icosahedral, positive single stranded RNA (+ssRNA) Chief vectors: gnats, mosquitoes, flies, ticks. NOT spiders — repeated trick MCQ Antigenic shift possible because of segmented genome allowing reassortment. --- 13. POXVIRUSESIncorrect statement