Lecture 8 - Virology (Part 2) PDF

Lecture 8 — Virology (Part 2) Dr. Ed El Sayed NURS 342 Objectives Influenza Virus Coronavirus Hepatitis Viruses (A, B, C, D, E) MPox 1. Influenza ssRNA Enveloped Loading… Belongs to the Orthomyxoviridae family Three types: Influenza A, Influenza B and Influenza C Influenza A infects humans (adults,...

Lecture 8 — Virology (Part 2) Dr. Ed El Sayed NURS 342 Objectives Influenza Virus Coronavirus Hepatitis Viruses (A, B, C, D, E) MPox 1. Influenza ssRNA Enveloped Loading… Belongs to the Orthomyxoviridae family Three types: Influenza A, Influenza B and Influenza C Influenza A infects humans (adults, children), pigs and birds Influenza B mainly infects children Only influenza A has been responsible for worldwide pandemics and approximately two-thirds of human infections annually Influenza A is further subdivided according to two main proteins: hemagglutinin (H) and neuraminidase (N) Hemagglutinin is responsible for viral attachment to host cells There are many different types of H and N and any combination between them is theoretically possible (e.g. H1N1, H3N2, H5N1) Route of transmission is respiratory droplets (either directly or indirectly) Neuraminidase is responsible for the release of mature virus from one cell to infect another Loading… Influenza seasonality Symptoms of influenza infection are usually non-specific (malaise, fatigue, muscle aches, headaches, coughing, sneezing, sore throat, nausea/vomiting in children) Symptoms last 3-7 days, but an infected person can be asymptomatic or can shed the virus 1-2 days before symptoms appear and 1-2 days after the symptoms disappear In rare cases influenza can lead to pneumonia or myocarditis Staphylococcus is the main cause of secondary infection post influenza infection and is associated with high morbidity and mortality Influenza is a vaccine preventable infection - Specific antivirals: Treatment is generally supportive (fluids, antipyretics, analgesics) If specific antiviral treatment is used, it should be prescribed within 48 hours of symptom onset (maximum efficacy) Neuraminidase inhibitors: oseltamivir (oral), peramivir (parenteral), zanamivir (inhalation) - Older agents target hemagglutinin of the virus (e.g. amantadine) are no longer used because of resistance - Baloxavir is a cap-dependent endonuclease inhibitor (single dose) used in neuraminidase resistant influenza (absorption decreased if co-administered with divalent cations) 2. SARS-CoV ssRNA Severe Acute Respiratory Syndrome (SARS) - Coronavirus 1 and 2 Enveloped Belongs to Coronaviridae family (named after the “corona” or “crown” shaped envelope proteins Middle Eastern Respiratory Syndrome (MERS) is a related agent SARS-CoV 1 and 2 require ACE2 receptor on host cell for entry Transmission is via aerosol respiratory droplets (direct or indirect) Loading… COVID19 is a vaccine preventable disease Vaccine preventable disease Remdesivir and molnupiravir are polymerase inhibitors The ONLY drug that clearly lowers COVID19 mortality is Higher mortality in older patients, and those with chronic disease (diabetes, kidney disease) or immunocompromised (cancer/chemotherapy) Nirmatrelvir + Ritonavir combo — protease inhibitor Azithromycin is ineffective against the virus! Hydroxychloroquine is ineffective against the virus! Monoclonal antibodies are for those who can not take the vaccine or not responding to medications Most symptoms are non-specific: “Long-COVID” — lingering chronic symptoms (most commonly residual cough and mental “fog”) thought to be due sustained low grade inflammation in the body Preventive measures are crucial because they are effective: Muscle aches, headaches, fever, cough Symptoms that are more specific to SARS-CoV2: Ageusia (loss of sense of taste), Anosmia (loss of sense of smell) Physical distancing Isolation when sick Masking indoors (but not cloth masks; the most effective are respirators e.g. N95 that is PROFESSIONALLY fitted) 3. Hepatitis A Virus (HAV) ssRNA Non-enveloped Belongs to Picornaviridae family Major route of transmission is oral-fecal (e.g. contaminated foods) Sexual transmission possible (oral sex) HAV targets the hepatocytes lliver) < need to have The virus enters the cell by endocytosis - NO liver specific receptor celly HAV is a vaccine preventable infection (pre and post exposure) In immunocompetent persons, infection is self-limiting and supportive treatment is enough (i.e. no specific antiviral therapy) Infection is characterized by jaundice and acute symptoms (nausea, vomiting, diarrhea) and elevation of liver enzymes * viral increases ↳ & => Peak * antibody body produce week I 19 iX IgM show recently * pt id , infected look at ALT IGM exposed E 4. Hepatitis B Virus (HBV) A , C, D UNI DNA virus (the only hepatitis virus that is DNA, all others are RNA) ↓ Enveloped (need receal Belongs to Hepadnaviridae family Blood borne pathogen (main route of transmission) Sexual transmission common Vertical transmission of HBV possible (of all viral hepatitis infections, num- baby HBV carries the HIGHEST risk of vertical transmission) ACE2 Main target is liver, enters individual hepatocyte via the sodium SARSCOV taurocholate co-transporter peptide (NTCP) Global distribution of HBV HBV enters the nucleus of the cell to form cccDNA (circular covalently closed DNA) The viral particle consists 3 main antigens: These biomarkers are used for screening, diagnosing, and treating the infection Surface antigen (HBsAg) Core antigen (HBcAg) e antigen (HBeAg) The immune system of the infected individual makes corresponding antibodies (HBsAb, HBcAb and HBeAb) HBV Serology Result Interpretation HBsAg HBcAb HBsAb Negative Negative Positive Uninfected but vaccinated, immune to infection Negative Negative Negative Never been infected, unvaccinated, and susceptible to infection HBsAg HBcAb HBsAb Active infection If sAb is HBsAg HBcAb HBsAb Positive Positive Positive IgM (acute) If sAb is IgG (chronic) HBsAg HBcAb HBsAb Negative Positive Positive Immune due to past infection HBV is a vaccine preventable infection HBV is a major cause of liver fibrosis, cirrhosis and hepatocellular carcinoma Treatment goals: Infection results in chronic disease (no cure) Higher chance of spontaneous clearance if infection acquired in adulthood Normalize liver function Make eAg negative Make viral DNA undetectable HBV treatment is with one drug (i.e. monotherapy effective) Treatment is usually lifelong Tenofovir Entecavir Lamivudine These drugs act as polymerase inhibitors and reverse transcriptase inhibitors that important Not When is interferon the answer for HBV? In other words, there is no such thing as HDV “mono-infected” patient So… is HDV a vaccine preventable infection? m - In the setting of = HDV coinfection HDV is ssRNA virus but cannot make its own envelope (must borrow the envelope protein from HBV) ↓ always infected wh HBU protected also protected ↑ so means B from 5. Hepatitis C Virus (HCV) ssRNA Vertical transmission of HCV is higher in the setting of HIV coinfection Enveloped Belongs to Flaviviridae family Blood borne pathogen (main route of transmission) Sexual transmission depends on the type of sex: transmission via oral and vaginal sex is very rare; but in the setting of HIV coinfection, transmission of HCV via anal sex is possible Global distribution of HCV The main target is liver HCV does not enter the nucleus of the cell Acute symptoms are non-specific and dissipate quickly, after that the virus replicates in the liver for decades (chronic infection) HCV is a major cause of liver fibrosis, cirrhosis and hepatocellualr carcinoma There is no vaccine against HCV or pre-exposure prophylaxis Entry of virus into individual hepatocyte is thought to be mediated by the LDL receptors There are over 10 genotypes of HCV: most common in US is genotype Loading… 1 The viral polymerases (NS5A and NS5B) build proteins necessary for replication The protease cuts the chunky proteins into small functional ones Four combos: HCV treatment is based on inhibiting at least two enzymes (i.e. monotherapy is ineffective) Ledipasvir/Sofosbuvir Velpatasvir/Sofosbuvir Pibrentasvir/Glecaprevir Elbasvir/Grazoprevir Interferon for HCV is WRONG! Lower chance of spontaneous clearance if infection is acquired in adulthood HCV screening is done by looking for antibodies against the virus So how to we know if the person is really infected? By looking for HCV RNA (aka “reflex” RNA) However, the mere presence of antibodies is NOT proof of infection This is because once infected, patents become antibody positive for life, even if they clear the infection Ab+ PLUS RNA detected = Infected Ab- = Never been infected OR very recently infected (check Ab+ BUT RNA undetected = Previous infection (cleared or cured) HBV vs HCV screening HBV: All adults aged 18+ Pregnant women (with every pregnancy) History of HIV infection, incarceration, injection drug use, homelessness, men who have sex with men, transgender men and sex work HCV All adults aged 18+ History of HIV infection, incarceration, injection drug use, men who have sex with men, transgender men and sex work HBV vs HCV HBV HCV DNA virus RNA virus Enters the nucleus (forms cccDNA) Remains in cytoplasm Vaccine preventable No vaccine Incurable with drugs Curable with drugs Monotherapy effective Monotherapy ineffective Higher transmissibility vs HCV via needle injury Lower transmissibility vs HBV via needle injury Higher risk of vertical transmission vs HCV Lower risk of vertical transmission vs HBV Possible transmission via vaginal sex Negligible transmission via vaginal sex Higher chance of spontaneous clearance if virus is Lower chance of spontaneous clearance if virus is acquired in adulthood acquired in adulthood 6. Hepatitis E Virus (HEV) ssRNA No vaccine non-enveloped (?) Belongs to Hepeviridae family Water-bone virus Endemic in South America, North Africa and Asia WORST viral hepatitis infection to get in pregnancy — high maternal and fetal mortality 7. Monkeypox dsDNA, enveloped virus Belongs to Poxviridae family Zoonotic virus, but “monkeypox” is misnomer because animal reservoir is large and includes squirrels, rats, mice Primary route of transmission is through close contact with body fluids harboring the virus from an infected animal or person Resurgence and outbreaks in the US primarily among transgender women and men who have sex with men Treatment: Tecovirimat (prevents viral release from infected cells) Vaccine: Only among persons at increased risk for infection Cervical (L) and Axial (R) Lymphadenopathy in Mpox Infection