Microbiology - Viruses IV: Covid-19, Childhood, and Enteric Tract Viruses PDF

Viruses IV – COVID-19, Childhood, and Enteric Tract Viruses PHA3109 Microbiology & Immunology Q3 2025 CHRIS BRACKETT PH.D. Overview COVID-19 Chapter 39: Important Childhood Viruses Chapter 40: Viruses that Infect the Enteric Tract  COVID-19 Features: ◦ COVID-19: SARS CoV-2: se...

Viruses IV – COVID-19, Childhood, and Enteric Tract Viruses PHA3109 Microbiology & Immunology Q3 2025 CHRIS BRACKETT PH.D. Overview COVID-19 Chapter 39: Important Childhood Viruses Chapter 40: Viruses that Infect the Enteric Tract  COVID-19 Features: ◦ COVID-19: SARS CoV-2: severe acute respiratory syndrome coronavirus 2 ◦ Single-stranded RNA genome; enveloped ◦ Origins unknown (likely not the seafood market); may have originated in animals (bats) ◦ Genetically similar to other coronaviruses (SARS-CoV and MERS-CoV) that can infect non- human primates and other animals ◦ Genome encodes large protein cleaved into ACE2: angiotensin-converting enzyme 2 non-structural proteins engaged in RBD: receptor binding domain transcription and replication Diagnosis: ◦ Nucleic acid amplification test (repeated Transmission: swabs) ◦ Airborne, transplacental (one case), ocular, ◦ Chest CT fecal, direct contact via fomites ◦ Serologic antibody detection https://www.nature.com/articles/s41579-020-00459-7 COVID-19 Components: ◦ S protein: viral spike protein of COVID- 19 ◦ TMPRSS2: transmembrane protease serine protease 2 in humans; exists in many tissues, often with ACE2 ◦ RdRp: RNA-dependent RNA polymerase of COVID-19 ◦ 3CLpro: 3C-like protease, a cysteine protease of COVID-19 ◦ Endosome: membrane-bound vesicle that facilitates viral entry and release in cytosol of host cell (other viruses enter this way, too) COVID-19 Pathogenicity: ◦ SARS-CoV-2 binds angiotensin-converting enzyme-2 (ACE2) receptor in humans, pig, ferret, rhesus monkey, civet, cat, and others ◦ The 211-amino acid region RBD binds ACE2 receptor and facilitates virus entry ◦ Target of neutralizing antibodies ◦ Virus binds respiratory tract epithelial cells where viral replication occurs. Infection migrates to alveoli in lungs which triggers an immune response (cytokine storm) leading to respiratory distress, respiratory failure and eventually death Consequences: ◦ Histopathology indicates bilateral alveolar damage ◦ Desquamation of pneumocytes ◦ Fibrin deposits ◦ Exudative inflammation COVID-19  COVID-19 Treatment Treatment: ◦ Inhibitors of Virus Replication Drug Mechanism Considerations Remdesivir Inhibits COVID-19 RdRp, FDA initially authorized for treatment preventing proteolysis of viral of hospitalized patients with severe polypeptides COVID-19. Later broadened to include non-hospitalized patients at risk for developing severe COVID-19 Nirmatrelvir/ Nirmatrelvir inhibits SARS- FDA granted authorization for the Ritonavir Cov-2 3CLpro cysteine treatment of mild to moderate COVID- (Paxlovid) protease, while ritonavir 19 in patients 12 and older. inhibits the metabolism of Not authorized for prevention or post- nirmatrelvir through CYP3A4 exposure prevention inhibition COVID-19 Prevention: Pfizer-BioNTech vaccine: mRNA-LNP, lipid nanoparticle-encapsulated nucleoside-modified mRNA vaccine, “modRNA”, that encodes COVID spike protein ◦ Modified RNA is suspended in lipids to facilitate host cell membrane fusion ◦ Devoid of preservatives Moderna vaccine: mRNA-1273 ◦ mRNA vaccine that encodes COVID spike protein ◦ Contains lipids ◦ Devoid of eggs, latex, preservatives Childhood Viruses Measles Measles Rubella Mumps Vaccination available Rubella Parvovirus Human herpesvirus 6  Childhood Viruses Human Measles Mumps Rubella Parvovirus Property Herpesviru Virus Virus Virus B19 s-6 Virus Paramyxoviru Paramyxoviru Togavirus Parvovirus Herpesvirus family ses ses Single- Single- Single- stranded Single- Double- stranded stranded Genome RNA; stranded stranded RNA; negative RNA; positive negative DNA DNA polarity polarity polarity Virion RNA Yes Yes No No No polymeras e Nucleocap Helical Helical Icosahedral Icosahedral Icosahedral sid  Childhood Viruses Rash Is a Causes Infection Causes Vaccine Promine Congenital Virus Disease Lifelong Immunity Availab Treatment nt Malformati to Disease le Feature ons Measles No antiviral Measles Yes No Yes Yes virus drug Mumps No antiviral Mumps No No Yes Yes virus drug Rubella No antiviral Rubella Yes Yes Yes Yes virus drug Slapped cheeks Parvovirus No antiviral syndrome; Yes Yes Yes No B19 drug hydrops fetalis No. Reactivation of Human latent infection No antiviral Childhood Viruses - Measles Causes maculopapular rash: flat, red area of skin with small, confluent bumps Features: ◦ Single-stranded, negative sense RNA genome ◦ Enveloped ◦ Helical nucleocapsid ◦ One serotype Transmission: ◦ Respiratory droplets Childhood Viruses – Measles Pathogenesis: Virus infects upper respiratory tract cells, then moves to bloodstream In bloodstream, reticuloendothelial cells are infected; a second replication cycle occurs Virus is carried through the blood to the skin, where the rash occurs Rash results from cytotoxic T cells attacking measles virus-infected cells in the skin Fusion protein causes giant cell formation Childhood Viruses – Measles Clinical findings: ◦ Koplik’s spots: bright red lesions with white, central dot on buccal mucosa ◦ Maculopapular rash ◦ Complications: encephalitis, deafness, mental retardation. ◦ In pregnancy, increased risk of stillbirth Treatment and prevention: ◦ No antiviral therapy ◦ Live, attenuated vaccine Childhood Viruses - Mumps Causes salivary gland swelling Features: ◦ Single-stranded, negative sense RNA ◦ Enveloped ◦ Helical nucleocapsid ◦ Single serotype Transmission: ◦ Respiratory droplets Childhood Viruses - Mumps Pathogenesis: ◦ After infecting upper respiratory tract, virus spreads to salivary glands: parotid gland, testes, ovaries, pancreas, meninges (sometimes) Complications: ◦ Orchitis in postpubertal males can lead to sterility if bilateral ◦ Meningitis from Mumps is typically benign and self-limited Treatment and Prevention: ◦ No antiviral therapy ◦ Vaccination with live, attenuated vaccine Childhood Viruses - Rubella Causes rubella and congenital rubella syndrome, which is characterized by congenital malformations Features: ◦ One piece of single-stranded, positive-sense RNA ◦ No virion polymerase ◦ Icosahedral nucleocapsid ◦ Lipoprotein envelope Transmission: ◦ Respiratory droplets; transplacental Childhood Viruses - Rubella Pathogenesis: ◦ Initial viral replication occurs in nasopharynx, local lymph nodes ◦ Virus spreads via bloodstream to skin, internal organs ◦ Maculopapular rash origin uncertain, but may be from antibody-antigen vasculitis ◦ Fetal harm may be profound if Mom is infected during the first trimester; shedding from Baby may occur for months Treatment and prevention: ◦ No antiviral therapy ◦ Live, attenuated vaccine available ◦ For pregnant women, serum immunoglobulins Rubella—note fine, almost confluent may be given macular-papular rash. Childhood Viruses – Parvovirus B19 Causes erythema infectiosum (fifth disease), slapped cheek syndrome, aplastic anemia, fetal infections (hydrops fetalis) Childhood Viruses – Parvovirus B19 Features: Pathogenesis: ◦ Very small (22 nm) ◦ B19 infects erythroblasts (red blood ◦ Nonenveloped cell precursors) in bone marrow and endothelial cells in blood vessels ◦ Single-stranded, negative strand DNA genome ◦ Immune complexes contribute to rash and arthritis ◦ No virion polymerase ◦ Icosahedral capsid Hydrops fetalis: ◦ One serotype B19-infected erythroblasts in fetus die  congestive heart failure  massive edema Transmission: ◦ Respiratory route; transplacental Infection in 1st trimester  fetal death Infection in 2nd trimester  hydrops fetalis Infection in 3rd trimester  no negative outcomes Childhood Viruses – Human Herpesvirus 6 Causes roseola infantum: disease characterized by rapid onset high fever that persists for days When fever subsides, macular or maculopapular rash appears Pathogenesis: ◦ Infects B and T cells; remains latent except in immunocompromised patients  pneumonia, hepatitis, encephalitis ◦ May cause encephalitis in stem-cell transplant recipients Transmission: Incompletely understood; may be via saliva, nasal, sexual transmission Treatment and prevention ◦ No antiviral drug for immunocompetent children ◦ No vaccine ◦ Ganciclovir for immunocompromised patients Enteric Tract Viruses Norovirus Rotavirus Transmitted by fecal-oral Poliovirus All are naked nucleocapsids (not route Coxsackie enveloped) All have RNA genome Echovirus Enteric Tract Viruses Property Norovirus Rotavirus Poliovirus Coxsackle Echovirus Virus Virus Caliciviruses Reoviruses Picornavirus Picornavirus Picornavirus Family Single- Double- Single- Single- Single- stranded stranded stranded stranded stranded Genome RNA; RNA; 11 RNA; RNA; RNA; positive segments positive positive positive sense sense sense sense Virion RNA No Yes No Polymeras e Nucleocaps Icosahedral Icosahedral Icosahedral Icosahedral Icosahedral id Envelope No No No No No Number of >2 >6 3 Many Many  Enteric Tract Viruses Virus Disease Main Clinical Findings Vaccin Antivi e ral Availab Thera le py Norovir Gastroenteritis Watery diarrhea No No us Rotavir Gastroenteritis Watery diarrhea Yes No us Poliovir Poliomyelitis Paralysis due to death of motor Yes No us neurons Coxsac 1. Hand, foot, and mouth 1. Vesicular lesions on hands, feet No No kie disease and mouth virus 2. Meningitis 2. Fever, headache, and stiff neck 3. Myocarditis 3. Congestive heart failure Echovir Meningitis Fever, headache, and stiff neck No No Viral Infection In general these viruses: ◦ Infect superficial epithelium of small intestine ◦ Destroy cells ◦ Disrupt absorption ◦ Cause water and electrolyte secretion, which causes osmotic (secretory) diarrhea Viruses that elicit GI effects: 1) Norovirus 2) Rotavirus Compared to bacterial infections, viral infections cause less severe effects, less severe complications Worldwide, ~20% of acute gastroenteritis results from norovirus. It infects 685 million worldwide. ~50,000 deaths per year, mostly in developing countries. Viral Infection - Norovirus Nonenveloped RNA genome, no polymerase One of the most common causes of viral gastroenteritis amongst adults, worldwide and in U.S. ◦ Rotavirus is the most common cause for children Transmitted by fecal-oral route, from ingestion of contaminated seafood or water Outbreaks may occur on cruise ships, in camps, hospitals, schools, and nursing homes http://www.epa.gov/nerlcwww/norwalk.htm Viral Infection - Norovirus The virus, itself, enhances infection: 1. Low infectious dose 2. Viral excretion in the stool BEFORE symptom onset AND AFTER recovery for several weeks 3. Resistant to chlorination 4. Resistant to desiccation 5. May stay infectious for days in water, uncooked food, and fomites Viral Infection - Norovirus Mechanism of Infection: Diagnosis: ◦ Not entirely understood ◦ Stool PCR Symptoms: Treatment: ◦Vomiting, headaches, ◦ Supportive care: fluids, diarrhea avoid/treat dehydration ◦Afebrile Prevention: Complications: ◦ Hygiene practices ◦ Dehydration ◦ No vaccine available Viral Infection - Rotavirus Double-stranded RNA genome with leading to dehydration capsid but no envelope Diagnosis: Six serotypes of human rotavirus ◦ Stool antigen by enzyme-linked Causes viral gastroenteritis, assay or PCR especially in children ages 6-24 Treatment: months ◦ Supportive: fluids and electrolytes, Symptoms avoid, treat dehydration ◦ Incubation period is 1-3 days ◦ Mild-moderate fever Prevention: ◦ Vomiting ◦ Hygiene ◦ Frequent, watery stools ◦ Vaccination: Rotarix, RotaTeq ◦ Fever, vomiting abate on Day 2 ◦ Diarrhea persists for 5-7 days  Enteric Tract Viruses Virus Virulence Factors Pathogenesis Norovirus Low ID, viral excretion in stool before Confined to intestinal tract mucosal cells and after symptom onset, resistance to desiccation, chlorination Rotavirus Viral proteins inhibit cell RNA and Binds beta-adrenergic receptor, replicates protein synthesis, alter tropism in small intestine mucosal cells  excess (movement with stimuli) fluid and water secretion Poliovirus Uses and immunoglobulin-like protein Replication in oropharynx, small intestine, to bind host cell surfaces; causes in lymphoid tissue  CNS and death of cytolysis motor neurons, which causes paralysis of muscles innervated neurons Coxsackie NSPs inhibit autophagosomes- Group A: skin, mucous membranes; Group virus lysosomes, which prevents viral RNA B: heart, pleura, pancreas, liver degradation Both: meninges, motor neurons  paralysis Summary COVID-19 Chapter 39: Important Childhood Viruses Chapter 40: Viruses that Infect the Enteric Tract