Naked RNA Viruses - Virology Lecture Notes PDF

Naked RNA Viruses A STUDENT ASKED HOW WE ERADICATED SMALLPOX, & WOULD IT WORK FOR MONKEYPOX? MODULE REVIEW WHY SHOULD YOU CARE? NAKED RNA VIRUSES WHY YOU SHOULD CARE: NAKED RNA VIRUS WHY YOU SHOULD CARE  CLASS OBJECTIVES  Be able to differentiate naked & enveloped RNA viruses, and how they d...

Naked RNA Viruses A STUDENT ASKED HOW WE ERADICATED SMALLPOX, & WOULD IT WORK FOR MONKEYPOX? MODULE REVIEW WHY SHOULD YOU CARE? NAKED RNA VIRUSES WHY YOU SHOULD CARE: NAKED RNA VIRUS WHY YOU SHOULD CARE  CLASS OBJECTIVES  Be able to differentiate naked & enveloped RNA viruses, and how they differ from DNA viruses in terms of structure, replication, morphology, etc. (ongoing)  Be able to define “sense”  Be able to compare & contrast naked & enveloped RNA viruses  Be able to distinguish which viruses are naked RNA viruses and the diseases they cause  Be able to diagnose the naked RNA viruses based on signs, symptoms, diagnostic tests  Be able to prescribe appropriate prevention and treatments including available vaccinations & therapeutics  Useful website: https://www.amboss.com/us/knowledge/General_virology *the commentary on no arms & no legs is ABLEISM language and not appropriate + Astroviridae- causes self-limiting gastroenteritis in children, especially with compromised immune systems Virus Family Caliciviridae Picornaviridae Reoviridae RNA Strand ssRNA ssRNA dsRNA RNA Shape Linear Linear Linear RNA Sense Positive Positive N/A b/c 1 of each Capsid Shape Icosahedral Icosahedral Icosahedral Important Enterovirus, Poliovirus, Rotavirus, Orthoreovirus, Examples Norwalk/Norovirus Rhinovirus, Coxsackie Coltivirus NAKED RNA VIRUSES  VIRAL LIFE CYCLE- ATTACHMENT & ENTRY  Recognize & Attach & bind to their specific receptors  Naked: surface-exposed capsid regions/proteins mediate attachment  Penetration- Virion moves along host cell surface where it encounters entry receptors (aka co-receptors)  Endocytosis & then virus is uncoated inside cell  Viropexis (Picorna, papilloma, & polyoma)- attach to cell & “phagocytized”  https://www.youtube.com/watch?v=D9 OtJU3F6eQ  Uncoating: virions disassembled. Capsid is removed to make viral genome accessible to cellular transcription & translation machinery  Most RNA viruses remain in cytoplasm  REPLICATION & RNA “SENSE”  Most RNA viruses replicate in cytoplasm (exceptions include influenza & retro)  dsRNA (Reo/Rota)  Viral RNA polymerase transcribes +ssRNA then translated to proteins  ssRNA Classified according to the polarity of their RNA  Positive-sense strand act as mRNA & are directly translated by cellular Naked positive-sense viral genomes are infectious ribosome to produce viral Naked negative-sense strand viral genomes are not infectious by themselves. proteins (Calici, picorna, astro) ASSEMBLY & RELEASE  Self-assembly of the genome and structural proteins produces the nucleocapsid  Assembly  Progeny viral RNA, early & late proteins, & capsid  Release  Usually lysis of the cell since they aren’t enveloped TEST YOUR KNOWLEDGE #1  What are the 3 virus families we’re going to learn today?  C- Caliciviridae  P- Picornaviridae  R- Reoviridae (Reo/Rota) CALICIVIRIDAE (NOROVIRUS)  CALICIVIRIDAE  Caliciviridae comprise single-stranded, positive sense RNA genomes  Round icosahedral shape with characteristic "spikes" on its surface  “Norwalk virus”- first name from 1970. First identified species  Now called Norovirus.  Sometimes referred to as the "winter vomiting bug" because it causes vomiting & during the winter months when we’re in close contact  NOROVIRUS  Norovirus is a leading cause of epidemic & sporadic gastroenteritis  Often thought of as "stomach flu," & is responsible for approximately 20 million cases of gastroenteritis in US per year  Vomiting, watery diarrhea, & stomach pain  Symptoms are typically self-limiting, & last ~3 days  However, illness may be more severe in very young or very old or immunocompromised  Transmitted via the fecal-oral route- Often in contaminated water or foods  Low infectious dose (relatively few virions can cause infection).  Prolonged viral shedding- Promotes transmission from host to host  Genetically diverse, so re-infection by different strains is possible  Prevention = good hygiene, including thorough hand washing; NO vaccine  No specific treatment, but rehydration therapy (administration of water & electrolytes) is recommended  FUN FACT: Alcohol based hand- sanitizers do not kill norovirus because it is a naked virus…. AKA WASH YOUR HANDS WITH SOAP & WATER PICORNAVIRUSES PATHOGENESIS OF PICORNAVIRUSES  A. 4 genera of picornaviruses include viruses that cause human disease  B. Genus Enterovirus consists of 10 species, of which 7 contain human pathogens: human enterovirus A–D & human rhinovirus A–C  Examples of each species are shown There are 81 non-polio & 3 polio enteroviruses that can cause disease in humans. Of the 81 non-polio types, there are 22 Coxsackie A viruses, 6 Coxsackie B viruses, 28 echoviruses, & 25 other enteroviruses  PHYLOGENETIC TREE Enterovirus A (formerly Human enterovirus A) Enterovirus B (formerly Human enterovirus B) Enterovirus C (formerly Human enterovirus C) Enterovirus D (formerly Human enterovirus D) Rhinovirus A (formerly Human rhinovirus A) Rhinovirus B (formerly Human rhinovirus B) Rhinovirus C (formerly Human rhinovirus C)  PATHOGENESIS OF PICORNAVIRUS  Infections with human enteroviruses A–D begin in alimentary tract; virus spreads through blood to target organs  Various clinical syndromes caused depending on target organ  Rhinovirus A-C infection initiates in mucosal epithelium in respiratory tract  Viral replication is limited to upper respiratory tract in A & B  Human rhinovirus C infections also involve lower respiratory tract  RHINOVIRUS (BE AWARE THAT MANY TEXTS CONTINUE TO REFER AS RHINOVIRUSES AS THEIR OWN GENUS)  Typically confined to upper respiratory tract  Recent evidence shows they can replicate in some portions of lower respiratory tract too  Limited range is due to need for lower temperatures for optimal replication  Infection of epithelial cells triggers the innate immune system  Inflammatory chemokines & cytokines contribute to “common cold” symptoms  Antibodies are produced but only provide transient protection against specific serotype responsible for infection  These antibodies are also insufficient against other serotypes   No vaccine (100s of serotypes)  Treatment is managing symptoms: NSAID (Advil), decongestant (pseudoephedrine, Sudaphed), expectorant (guaifenesin, Mucinex), bronchodilator (albuterol)  POLIOVIRUS  Poliovirus types 1-3  Usually asymptomatic, 1 in 200 cases will involve central nervous system (Poliomyelitis)  Virus reaches CNS via viremia & retrograde neuronal travel  Replicates in spinal cord (motor neurons of anterior horn)  Causes meningitis in some individuals  Symptoms:  Poliomyelitis-Temporary or permanent paralysis that typically involves limbs; can be fatal when muscles involving respiration are involved  Post-polio syndrome occurs when nerve dysfunction occurs 30-40 years after initial poliomyelitis  1961 1955 POLIOVIRUS TREATMENT & PREVENTION  Treatment  "Iron lung" = Emerson Respirator used to mechanically support respiration in polio patients  Prevention  Vaccination can prevent this crippling and potentially fatal disease  Inactivated polio vaccine (IPV) is currently given to children in the US & to adults at increased risk (travelers, laboratory & health care workers, etc.)  Live attenuated oral polio vaccine (OPV) is still available in some countries  COXSACKIE VIRUS  Coxsackieviruses A is associated with the following:  Herpangina = self-limiting acute febrile illness; Most commonly affects children  Fever, vomiting, & small painful lesions or ulcers in the mouth, i.e. oropharynx  Hand-foot-and-mouth disease= self limiting Oral sores & rash on hands & feet, & other nonspecific symptoms; most commonly affects children (LOL- Dr. D had it recently)  Coxsackieviruses B is associated with the following:  Pleurodynia (Bornholm disease)- Inflammation of pleura, often accompanied by fever  Patients experience mild-severe muscle pain in thorax & abdomen, especially during deep breathing; Usually self-limiting  Myocarditis, particularly in newborns  Paralysis (occasionally)  Type 1 Diabetes development via destruction of pancreatic islet cells REOVIRIDAE (& ROTAVIRUS) Reovirus- Respiratory, Enteric, Orphan)  ROTAVIRUS  "Wheel-like" morphology  Fecal-oral transmission- shed in feces  Severe diarrhea in children/infants  Can lead to death if dehydrated/malnourished  Rotaviruses have enterotoxin-like effects:  NSP4 protein increases enterocyte cytoplasm calcium concentration, which leads to changes in cytoskeleton  These changes disrupt membrane transport in ways that promote water & electrolyte loss (diarrhea)  Vaccine: Because rotavirus can cause severe morbidity or even death, rotavirus vaccine is recommended for all infants TEST YOUR KNOWLEDGE #2  You’re a doctor on a cruise ship to Mexico during spring break and you see an 18- year-old biologically female patient complaining of stomach pain, nausea, and vomiting.You suspect it could be a hangover, but after asking what the patient last consumed, she denies alcohol, but instead informs you she has been eating only at the salad bar… What might you suspect is her diagnosis?  Norovirus ALSO A SCIENTIST- THE WOMEN BEHIND THE POLIO VACCINE Isabel Morgan, PhD (1911-1996)  Throughout the 1940s Morgan worked with a team of virologists at Johns Hopkins University in the USA, advancing understanding of polio viruses. She and her team were the first to prove that an inactive or “killed” virus could produce immunity in monkeys, overturning the previous belief that only live viruses could do so.  Her work fed directly into the development of Jonas Salk’s vaccine against polio in 1955. She is also the only woman on the 17 person polio “wall of fame”. ALSO A SCIENTIST- THE WOMEN BEHIND THE POLIO VACCINE Dorothy Horstmann, MD (1911-2001)  Dr. Horstmann was an epidemiologist and virologist who showed that poliovirus reaches the brain through the blood. Her discovery enabled the development of a vaccine. She also became the first woman to be appointed a professor at the Yale School of Medicine.  Thanks to vaccines, polio has almost been eradicated, with cases down by more than 99% since 1988. International organisations like Rotary, Gavi and Global Polio Eradication Initiative are now helping countries finish the job with inactivated polio vaccine.