Week 3 Virology-Respiratory Hepatitis Retrovirus Papilloma Polyoma Viruses PDF

MABS Microbiology Virology: Respiratory, Hepatitis, Papilloma and Polyoma Viruses Human Retroviruses  Course Instructional Objectives MCRO 3.1 The student will describe the taxonomy, structure and function of the pathogenic human virus Coronavirus famil...

MABS Microbiology Virology: Respiratory, Hepatitis, Papilloma and Polyoma Viruses Human Retroviruses  Course Instructional Objectives MCRO 3.1 The student will describe the taxonomy, structure and function of the pathogenic human virus Coronavirus family: including transmission, pathogenesis, stages of viral infection, viral gene expression, viral replication, effects at.the cellular level and/or human immune response. MCRO 3.2 The student will describe the taxonomy, structure and function of the pathogenic human influenza virus of the Orthomyxoviridae family: including transmission, pathogenesis, stages of viral infection, viral gene expression, viral replication, effects at the cellular level, human immune response and/or treatment. MCRO 3.3 The student will describe the taxonomy, structure and function of the pathogenic human RSV virus Paramyxoviridae family: including transmission, pathogenesis, effects at the cellular level and/or human immune response. MCRO 3.4 The student will describe the taxonomy, structure and function of the pathogenic human virus Adenovirdae family: including transmission, pathogenesis, stages of viral infection, viral gene expression, viral replication, effects at the cellular level and/or human immune response. MCRO 3.5 The student will describe the taxonomy, structure and function of the pathogenic retroviruses, especially HIV-1: including transmission, pathogenesis, stages of viral infection, viral gene expression, viral replication, effects at the cellular level, human immune response and/or treatment. MCRO 3.6 The student will describe the taxonomy, structure and function of the pathogenic human virus Papillomaviridae family: including transmission, pathogenesis, stages of viral infection, viral gene expression, viral replication, effects at the cellular level and/or which forms of HPV are less/more likely to lead to cancer. MCRO 3.7 The student will describe the taxonomy, structure and function of the pathogenic human hepatitis viruses, especially HVA, HVB and HVC: including transmission, pathogenesis, stages of viral infection, effects at the cellular level and/or human immune response.  Review: Components of a Virus Viral Component Role in Viral Life Cycle Example Nucleic acid Encodes all the information necessary to DNA or RNA produce new progeny virions Red strings Capsid Protein “shell” that contains/packages viral Icosahedral, helical, or (rarely) nucleic acid, protecting it between infections; complex Small inner green and may contain VAP blue spheres Structural Proteins which form the capsid, package the Matrix, nucleocapsid, VP1-VP4 proteins genome, and/or are attachment proteins (reovirus), hexon and fiber Capsid + outer green (adenovirus), gp41/120 (HIV), stalks and large blue HA (influenza), F (measles) spheres Non-structural Proteins which are required for replication, for Polymerase, helicase, protease proteins assembly, or which facilitate disease (flu N), transcription factors, progression immunomodulatory factors Black beads Envelope Lipid bilayer which is an anchoring surface for viral attachment proteins, facilitates Orange coat penetration of the host cell membrane MCRO 2.1  Respiratory Viruses Introduction: Chapter 9 Respiratory disease accounts for an estimated 75% to 80% of all acute morbidity in the United States Most of these illnesses (approximately 80%) are viral infections, transmission typically be respiratory droplet (i.e.cough) or by hand transfer; incubation is 1-4 days but up to 14 days Although a majority of the episodes may not require medical attention, the overall average is three to four illnesses per year per person The viruses that are major causes of acute respiratory disease (ARD) include: influenza viruses parainfluenza viruses respiratory syncytial virus (RSV) coronaviruses (including COVID-19) adenoviruses rhinoviruses human metapneumovirus (hMPV) bocaviruses (a member of parvovirus group) Read: Sherris & Ryan Chapter 9 Common Respiratory Viruses  VAP and Cell Receptor Pairs Virus Family Structural Characteristics VAP Receptor Cell tropism HIV-1 Retroviridae ssRNA, positive sense, gp120 CD4 T cells, macs enveloped EBV Herpesviridae dsDNA, icosahedral, enveloped gp350, CD21 (CR2) B cells gp220 Rabies Rhabdoviridae ssRNA, negative sense, G protein Acetylcholine Neurons and enveloped receptor muscle Influenza Orthomyxoviridae ssRNA, negative sense, HA Sialic acid Respiratory segmented, enveloped epithelial cells Rhinovirus Picornaviridae ssRNA, positive sense, VP1,2,3 ICAM-1 Epithelial cells icosahedral, non-enveloped complex SARS-CoV-1 and Coronaviridae ssRNA, positive sense, Spike (E2) ACE2 (and other Many different cell SARS-CoV-2 enveloped protein proteins) types: esp. (COVID) epithelium of respiratory & GI Adenovirus Adenoviridae dsDNA, icosahedral, non- Fiber protein CAR Many different cell enveloped types Parvovirus B19 Parvoviridae ssDNA, icosahedral, non- VP1,2 Erythrocyte P Ag Erythroid precursor enveloped (globoside) cells MCRO 3.1  Summary: Coronaviruses Coronaviruses are the largest RNA viruses: Comprised of a positive-sense RNA genome, a helical nucleocapsid and a lipid bilayer envelope containing viral Spike (S) glycoprotein, membrane glycoprotein, and envelope glycoprotein. The virus replicates in the cytoplasm by using its newly synthesized viral RNA polymerase and assembles in the cytoplasm acquiring an envelope from ER-Golgi membranes Three novel human coronaviruses have been identified causing severe acute respiratory syndrome, SARS- CoV-1, MERS-CoV, and SARS-CoV-2 in 2019 (COVID-19). While SARS and MERS were highly fatal, approx. 10% & 35% respectfully, they were limited in spread and number of cases. COVID-19 became a pandemic infection involving most countries and causing 178 million cases and 3.86 million deaths globally SARS-CoV-2 is transmitted through respiratory droplets and its Spike glycoprotein interacts with ACE2 receptor in the upper and lower respiratory tract Molecular (RT-PCR) and antigen tests are available to detect SARS-CoV-2; antibody test for past exposure Read: Sherris & Ryan Citation: Chapter 9 Respiratory Viruses, Ryan KJ. Sherris & Ryan's Medical Microbiology, 8th Edition; 2022. Available at: https://accessmedicine.mhmedical.com/content.aspx?bookid=3107&sectionid=260923446 Accessed: January 23, 2024 Chapter 9 Copyright © 2024 McGraw-Hill Education. All rights reserved MCRO 3.1  Respiratory Epithelium § Upper Respiratory is respiratory tract above the larynx (voice box); i.e. sinuses, nasal cavity, pharynx the epithelium are taller epithelial cells with cilia and mucus-producing cells this functions to help clean inhaled air by trapping debris in the mucus and use the cilia to move this debris towards GI tract (acid in stomach can help neutralize debris § Lower Respiratory is respiratory tract below the larynx (voice box); i.e. bronchi, bronchioles & alveoli (air sacs in lungs) the epithelium become shorter & lose cilia/mucus- producing cells the shorter cells help promote better diffusion of oxygen & carbon dioxide MCRO 3.1  Respiratory Epithelium § SARS-CoV-2 enters via the respiratory tract and nasopharyngeal (upper respiratory tract) and/or oropharyngeal cells (start of GI tract) and are the initial targets for viral entry and replication. § This is followed by viral reproduction in airways and possibly moving towards lower respiratory tract of bronchial epithelium, alveolar epithelial cells and alveolar macrophages. § Viral Spike (S) glycoprotein’s RBD (receptor binding domains) binds to ACE2 receptor § ACE2 receptors are found in the respiratory system, kidney and myocardium of the heart. MCRO 3.1  Coronaviruses Family is Coronaviridae, linear positive sense ssRNA genome, enveloped, helical capsid Hallmark – an envelope with club-shaped protein peplomers forming a corona (crown, halo) around the viral capsid; these proteins also protect against acidic GI conditions (unique among enveloped viruses) Transmission – respiratory droplet, fecal-oral Viral attachment protein (VAP) – E2 or spike glycoprotein Tropism – respiratory tract or GI tract (epithelium) Production of multiple, individual mRNAs for protein production may contribute to generation of diversity Generation of many mRNAs at the same time that progeny genomes are being synthesized may promote recombination and introduce diversity into the genome MCRO 3.1 http://www.nature.com/nrmicro/journal/v11/n12/full/nrmicro3143.html  “Common” Coronavirus Disease Infects respiratory epithelium (tropism), disrupts cilia function on the epithelial cells of the respiratory tract Optimal growth temperature 100) which produce different diseases. Pathology of Infectious Diseases. Stamford CT: Appleton & Lange; 1997.) Lytic, latent, and transforming infection possible. Determined by infecting strain. Read: Sherris & Ryan Chapter 19 Citation: Chapter 19 Papilloma and Polyoma Viruses, Ryan KJ. Sherris & Ryan's Medical Microbiology, 8th Edition; 2022. Available at: https://accessmedicine.mhmedical.com/content.aspx?bookid=3107&sectionid=260925383 Accessed: January 23, 2024 MCRO 3.6 Copyright © 2024 McGraw-Hill Education. All rights reserved  HPV Strains and Disease Associations Syndrome Human Papillomavirus Types Common Less Common Cutaneous Syndromes Skin Warts Plantar wart 1 2, 4 Common wart 2, 4 1, 7, 26, 29 Flat wart 3, 10 27, 28, 41 Epidermodysplasia verruciformis 5, 8, 17, 20, 36 9, 12, 14, 15, 19, 21-25, 38, 46 Mucosal Syndromes Benign Head and Neck Tumors Laryngeal papilloma 6, 11 — Oral papilloma 6, 11 2, 16 Conjunctival papilloma 11 — Anogenital Warts Condyloma acuminatum 6, 11 1, 2, 10, 16, 30, 44, 45 Cervical intraepithelial neoplasia, cancer (high- 16, 18 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 66, risk types) 68, 69, 73, 82 Medical Microbiology, Murray, et. al., 9th ed. 2021, Table 41-2 MCRO 3.6  HPV Epidemiology SEE NOTES HPV is ubiquitous Disease Strains Transmission – virions are stable and resist inactivation → Plantar wart 1 Common wart 2, 4 transmitted on fomites such as countertops, furniture, bathroom Laryngeal papilloma 6, 11 floors, towels as well as by close personal contact Condyloma acuminatum 6, 11 Common, plantar, and flat warts are most common in children and Cervical carcinoma 16, 18, 31, 33 young adults Sexual transmission for most medically imp. strains http://l7.alamy.com/ zooms/7eeacc6c22 9543f6933340e721 – May be most common STI 861fdb/common- wart-caused-by- hpv-human- – HPV present in >99% of cervical cancers papilloma-virus- a8je7m.jpg – 5% of PAP smears contain HPV – 10% of women infected with “high-risk” strains develop cervical dysplasia (precancerous state) – Risk factors for disease progression – family history, multiple sexual partners, smoking, immunosuppression http://webeye.ophth.uiowa.edu/eyeforum/atlas/pages/Conjunctival-papilloma/conj-papilloma-LRG.jpg MCRO 3.6  HPV Transformation E5, E6, and E7 are oncogenes (oncogenes make malignancy more likely as leads to uncontrolled cell growth/cell division) – E5 = stabilizes cellular epidermal growth factor (EGFR), making it more sensitive to growth signals – E6 = binds p53 and targets it for degradation by host ubiquitin proteosome pathway – E7 = binds and inactivates pRb Actions of E5, E6, and E7 increase cellular proliferation and prevent DNA repair Results – increased risk of cells with mutations or chromosomal damage → No viral replication in transformed cell, so That, in turn, increases the potential for the cell’s energy goes to hyperproliferation transformation à cancer http://immunopaedia.org.za/index.php?id=799 MCRO 3.6  HPV Transformation FIGURE LEGEND – Integration of the HPV genome with a disrupted E2 gene into host chromosomal DNA is a necessary event that can lead to the development of carcinoma. The E2 gene encodes a transcription factor that regulates the transcription of HPV E6 and E7 oncoproteins. In the absence of E2, increased synthesis of E6 and E7 protein occurs. E6 binds to p53 in the cytosol and also recruits the E6AP ubiquitin ligase that ubiquitinates p53 and targets it for proteosomal degradation. Similarly, HPV E7 binds to pRb in the cytosol and recruits the cullin 2 ubiquitin ligase that ubiquitinates pRb and promotes proteosomal degradation. Loss of cellular p53 and pRb tumor suppressor proteins allow a cell with DNA No viral replication in transformed cell, so damages to divide and thereby increases the risk of the cell’s energy goes to hyperproliferation cancer development. http://immunopaedia.org.za/index.php?id=799 MCRO 3.6  HPV Diagnosis Medical Microbiology, Murray, et. al., 9th ed. 2021, Figures 41-7 (top) and 41-4 (bottom) Microscopically – Excess production of keratin – hyperkeratosis – Koliocyte = enlarged keratinocyte with clear halo (vacuolization) around nucleus. Seen with ALL serotypes of HPV! – Papanicolaou-stained cervical smears (Pap smears) Very defined cellular and cytologic changes Grading system – more in block 6 MCRO 3.6 http://www.hpvinformation.com/~/media/TheHPVTest/Images/FAQs/CervicalCancerEducational.ashx Hepatitis Viruses: hepatitis (inflammation of the liver) Diverse/Different Families, most are RNA viruses (except Hepatitis B) MCRO 3.6  Hepatitis Viruses Liver Inflammation Causes: Viral (A, B, C, D, E) Alcoholic Ischemic Autoimmune MCRO 3.6  Hepatitis Viruses Virus Family Virology Disease Hepatitis A Picornavirus, Fecal-oral; short incubation Acute hepatitis (fever, jaundice, increased ALT RNA (~1m); not a chronic carrier and AST); asymptomatic or mild disease; abrupt onset Hepatitis B Hepadnavirus, Sexual, maternal-fetal; long Recurrent hepatitis; integrates into host DNA incubation (~3m); chronic carrier genome; risk of hepatocellular carcinoma and cirrhosis; potentially severe disease Hepatitis C Flavivirus, RNA Blood; long incubation; chronic Recurrent hepatitis; cirrhosis; risk of carrier hepatocellular carcinoma due to chronic inflammation; generally subclinical disease Hepatitis D Deltavirus, RNA Parental, sexual, maternal-fetal; Cirrhosis; fulminant hepatitis; dependent on (see notes) short incubation (HDV after HBV co-infection; occasionally to often severe HBV) or long incubation (HDV disease; high mortality rate; abrupt onset with HBV); chronic carrier Hepatitis E Hepevirus, Fecal-oral; no chronic infection Acute and epidemic hepatitis; high mortality in RNA pregnant women; abrupt onset Hepatitis G Flavivirus, RNA Chronic infection MCRO 3.6  Hepatitis Overview Disease can range from asymptomatic and self- http://emedicine.medscape.com/ limiting acute infection to severe acute infection to article/177484-overview#a0104 chronic infection – depends upon infecting virus Common features – Much, and sometimes all, of disease symptoms result from host immune response – General disease progression Prodrome – fever, malaise, anorexia Pre-icteric – nausea, vomiting, abdominal pain, fever, chills Icteric – jaundice, dark urine, increased ALT and AST levels Diagnosis is based upon time course of symptoms, patient history, and/or serology for viral Ag or virus- specific Ab http://www.ok.gov/health/Disease,_Prevention,_Preparedness/ Acute_Disease_Service/Disease_Information/Hepatitis_A.html MCRO 3.7  Hepatitis A Virus (HVA) Picornaviridae family, positive sense ssRNA, icosahedral Non-enveloped capsid provides stability, including resistance to stomach pH and heat Acquired by ingestion – contaminated food (shellfish) or water At-risk populations – travelers and day care Initial replication in intestinal epithelium before hematogenous dissemination to liver Spread of hepatitis A virus within the body. Replicates in hepatocytes and Kupffer cells (macrophages in the liver) with minimal damage Replicates in the cytoplasm by using viral RNA polymerase Read: Sherris & Ryan Chapter 13 Virus shed in stool for at least 10 days before onset of Medical Microbiology, Murray, et. al., 9th ed. 2021, Figure 55-2 symptoms MCRO 3.7  Hepatitis A Virus no chronic sequelae (self- limited disorder; i.e. does not typically result in a chronic disease) humans only known reservoir fecal-oral transmission Read: Sherris & Ryan Chapter 13 Medical Microbiology, Murray, et. al., 9th ed. 2021, Figure 55-2 MCRO 3.7  Hepatitis C Virus (HVC) Flaviviridae family, positive sense ssRNA genome, enveloped 6 major genotypes (7 for 1a & 1b); different geographic distributions RDRP (RNA-dep. RNA pol.) – no proofreading ability, so very high mutation rate that gives rise to HCV quasi-species that escape established HCV- specific Ab and CTL responses Tropism – hepatocytes, possibly B cells At least 50% of hepatocytes infected in patient with chronic HCV hepatitis Transmission – transfused blood and Structure of hepatitis C virion. Inside the icosahedral core is a single-stranded, transplanted organs, sexual positive-sense RNA enclosed in a lipid bilayer membrane containing viral specific glycoproteins, E1 and E2. E2 glycoprotein interacts with the receptor on the host cells. MCRO 3.7  Hepatitis C Virus FIGURE LEGEND – (1) HCV binding (CD81 antibodies could prevent HCV binding). (2) Entry via receptor-mediated endocytosis. (3) Fusion of the viral envelope and a cellular membrane leads to uncoating and release of the viral RNA. (4) Translation of the viral RNA in the rough ER (protease inhibitors could inhibit polyprotein processing). (5) The nonstructural protein, together with the viral RNA and probably host factors, form the replication complex in the vesicular membrane structures (replication can be affected by a range of agents, including NS5B polymerase inhibitors). The replication complex catalyzes the amplification of the positive-strand RNA genome. (6) Virions undergo morphogenesis, (7) mature and (8) are released from the cell through the secretory pathway. The precise mechanism of action for NS5A inhibitors is unknown. Abbreviation: NS, nonstructural. http://www.nature.com/nrgastro/journal/v8/n2/full/nrgastro.2010.219.html MCRO 3.7  Hepatitis C Virus Disease 70-75% of infections become chronic with continuous, low-level production of virus Disease graded by extent of inflammation, lymphocytic infiltration, fibrosis (portal and periportal), and necrosis (lobular). Disease exacerbated and accelerated by excessive alcohol use or co-infection with HIV-1 or HBV. Medical Microbiology, Murray, et. al., 9th ed. 2021, Figure 55-14 MCRO 3.7  Hepatitis B Virus (HVB) General rule for hepatitis viruses: acute infection secretes IgM antibodies and if chronic, secretes IgG antibodies Hepatitis B (Serum Hepatitis or HBV) DNA virus, Hepadnavirus family Hepatocellular necrosis occurs due to the body’s reaction to the virus rather than due to the virus itself Acute Illness: jaundice Chronic Illness can result in: Cirrhosis, Hepatocellular carcinoma Transmission: many routes transfusion, transplant recipients mother-child blood exposure MCRO 3.7  Hepatitis B Virus (HVB) Schematic diagram of hepatitis B virion. A. The 42 nm particle is the “Dane particle” or the hepatitis B virus. B. The 22-nm particles are the filamentous and circular forms of hepatitis B surface antigen (HbsAg) or protein coat. (Reproduced with permission from Nester EW, Anderson DG, Roberts CE Jr, et al: Microbiology: A Human Perspective, 6th ed. New York, NY: McGraw Hill; 2008.) Citation: Chapter 13 Hepatitis Viruses, Ryan KJ. Sherris & Ryan's Medical Microbiology, 8th Edition; 2022. Available at: https://accessmedicine.mhmedical.com/content.aspx?bookid=3107&sectionid=260924153 Accessed: January 23, 2024 MCRO 3.7 Copyright © 2024 McGraw-Hill Education. All rights reserved