Virology 5: Plus (+) Strand RNA Viruses

How long can people with Norovirus shed the virus after their symptoms resolve?

2 weeks

Who is primarily affected by Coxsackievirus?

Infants and young children - during summer months

Why are Coronaviruses a concern for a possible pandemic outbreak?

It is a zoonotic (animal reservoir) virus that has had several large outbreaks recently -SARS (China) -MERs-CoV (Middle East)

Can we treat/vaccinate against Norovirus?

No, just wait it out and rehydrate

What's the difference between non-paralytic and paralytic polio?

Non-Paralytic Poliomyelitis - 1-2% - CNS and meninges infected → back pain, muscle spasm Paralytic Polio - 0.5-2% - anterior horn of spinal cord and motor cortex of brain → paralysis

Picornaviruses characteristics and pathogens

Plus (+) strand RNA viruses non-enveloped important human pathogens: -Enterovirus --- (A and B), Echovirus, Enterovirus D68 -Rhinovirus -Hepatovirus ---Hepatitis A virus

What family is the Rotavirus a member of?

Reovirus Family (Respiratory, Enteric, Orphan)

What are 3 virus families that cause upper respiratory infections?

Rhinovirus, Coronavirus, Adenovirus

T/F: You can be reinfected by norovirus because of the high number of strains and high mutation rate

True

What are the origins and symptoms of SARS-CoV-2?

Wuhan, China - bats -> ? -> humans, person to person via respiratory droplets mild to severe symptoms

Can Rotavirus be vaccinated against?

Yes (2 vaccines available)

Structure of Rotavirus

ds RNA genome with 11 RNA segments non-enveloped, double layer capsids

Which of the following Plus (+) Strand RNA viruses was responsible for the Severe Acute Respiratory Syndrome (SARS) outbreak in China? a. Poliovirus b. Coxsackieviruses c. Norovirus d. Rotavirus e. Coronaviruses

e. Coronaviruses

________________________ is a Plus (+) Strand RNA virus that has an Enveloped Virion with club-like projections. They have a loosely helical nucleocapsid (due to association with N-protein). It causes upper respiratory infections in adults. a. Poliovirus b. Coxsackieviruses c. Norovirus d. Rotavirus e. Coronaviruses

e. Coronaviruses

Which of the following Plus (+) Strand RNA viruses causes at least half of the "common cold"s? a. Poliovirus b. Coxsackieviruses c. Norovirus d. Rhinovirus

e. Rhinovirus

How is poliovirus transmitted?

fecal-oral

How is norovirus transmitted?

fecal-oral resistant to heat, pH, detergent lasts 1-3 days, self-limiting, rehydration therapy as needed

What illness is Norovirus the leading cause of in the united states?

food-borne disease outbreaks

Which type of Coxsackievirus causes Herpangina (lesions on oropharynx) and Hand/Foot/Mouth Disease?

group A Coxsackieviruses

To whom is Coxsackievirus-caused Myocarditis most threatening to?

occurs in older children and adults sporadically, but most threatening to infants

What is the function of Viral Replicase (RDRP) in the replication cycle of Picornaviruses?

synthesizes complementary minus (-) strand of RNA which is used to make more plus strand

What are the symptoms of human coronaviruses?

upper respiratory infection (esp. adults) #2 for colds behind Rhinoviruses enteric infections (infants) rarely neuro

Rhinoviruses

can't replicate in GI tract (labile to acidic pH) - so not fecal-oral transmitted as aerosols, on fomites asymptomatic in many

How do we diagnose Norovirus?

- real time RT/PCR for viral RNA on stool, vomitus, environmental specimens - EIA assays when a group of people all got gastroenteritis (not sensitive enough for an individual)

What are the poliovirus vaccine recommendations in the US?

1. Attenuated vaccine is recommended -Infants= 4 doses -adults traveling to polio-endemic areas = 3 doses 2. OPV (oral attenuated) is NOT recommended bc possible vaccine associated disease

What is the pathogenesis of Poliovirus?

1. Enters mouth (enterovirus) 2. Replicates in pharynx, GI, and local lymphatics 3. Spreads to lymphatic system and CNS 4. Spreads along nerve fibers -destroys motor neurons

Where does poliovirus enter the body? Where does it replicate?

1. Mouth (enterovirus) 2. Pharynx, GI tract, and local lymphatics

What are the poliovirus vaccine recommendations in Developing Countries?

1. OPV (Oral Attenuated) is recommended 2. Inactivated vaccine is sometimes given in conjunction

SARS-CoV-2 Replication

1. its spike protein binds ACE-2 receptor → envelope peeled off → virus enters cell, RNA in cytoplasm 2. ORF1a/b RNAs made, translated into pp1a and pp1ab proteins 3. Protein pp1a, ppa1b cleaved by protease → 16 nonstructural proteins which can form RHA-dependent RNA polymerase (RdRp) which uses the (+) strand genomic RNA as a template 4. (+) strand genomic RNA produced through replication process becomes genome of new virus particle 5. Subgenomic RNAs → structural proteins, form viral particle 6. Spike, envelope, membrane proteins enter ER, nucleocapsid protein combined with (+) strand RNA to become nucleoprotein complex, merge into complete virus particle → excreted out cell

What are the symptoms of poliovirus?

90% asymptomatic, limited to oropharynx and gut 5% abortive poliomyelitis = fever, headache, etc. within 3-5 days of exposure

What is the importance of NSP4 protein to the symptoms of Rotavirus?

Acts in a Cholera Toxin-like fashion to cause diarrhea -Prevents water absorption causing loss of ions

T/F: Most poliovirus infections show symptoms

False (90% asymptomatic)

How are coxsackieviruses transmitted?

Fecal-oral

How is Rotovirus spread?

Fecal-oral (survives GI environment)

Which type of Coxsackievirus causes Myocarditis, Pleurodynia/Bornholm/Devils grip (fever and chest pain), and Aseptic Meningitis, in addition to fever/sore throat/rashes?

Group B

What are the origins and symptoms of SARS-CoV?

Guangdong, China - bats to other animals, human to human influenza-like, fever, malaise, myalgia, headache, diarrhea, shivering (rigors) fever can be absent initially in elderly/immunocompromised cough (initially dry), shortness of breath, diarrhea - can progress into respiratory distress

What are the 4 structural proteins of SARS-CoV-2?

S,E,M,N

What are the origins and symptoms of MERS-CoV?

Saudi Arabia - bats to camels, camels to humans ranges from asymptomatic to mild respiratory to acute respiratory and death GI symptoms as well in elderly/immunocompromised

How are coronaviruses transmitted?

aerosols and droplets, possibly mechanical

Which of the following Plus (+) Strand RNA viruses causes Hand, foot, and mouth disease? a. Poliovirus b. Coxsackieviruses c. Norovirus d. Rotavirus e. Rhinovirus

b. Coxsackieviruses

Replication Cycle of Picornavirus

binding b/w viral capsid protein and cell surface receptor via ICAM-1→ virion structure changes, viral plus strand RNA injected directly into cytoplasm → translation of single polyprotein and proteases - proteases cleave the polyprotein into diff proteins (capsid proteins, viral replicase (RDRP), VPg protein that binds to 5' end of RNA) VPs (0,1,3) protomers assembled → pentamers → procapsid viral RNA inserted into procapsid → VP0 cleaved into VP2 + VP4 → mature capsid Picornaviruses released via cell lysis (cytolytic)

________________________ is a small, round, non-enveloped, Plus (+) Strand RNA Virus that is known to cause Infectious Gastroenteritis in nursing homes. a. Poliovirus b. Coxsackieviruses c. Norovirus d. Rotavirus e. Rhinovirus

c. Norovirus

__________________ is a double-stranded RNA virus that is the MOST common cause of childhood diarrhea and gastroenteritis. Diarrhea is caused by Toxin-like activity due to NSP4 protein. a. Poliovirus b. Coxsackieviruses c. Norovirus d. Rotavirus e. Coronaviruses

d. Rotovirus (the only double stranded RNA!!!)