Roatviruses are the single most important etiologic agent of severe diarrheal illness of ________ worldwide, especially in undeveloped countries
infants and young children
What family does Rotavirus belong to?
Reo= respiratory, enteric, orphan
What is the structure of Rotavirus?
non-enveloped particles consisting of 2-3 concentric icosahedral capsids
What is the genome of Rotavirus?
segmented, double-stranded RNA with high antigenic diversity:
divided into 11G (VP7) and 12P (VP4) serotypes (note that 4 G-P combinations cause 90% of disease in humans- basis of success of vaccine)
What is the first step of the rotavirus replication cycle?
1. Virus taken up by endocytosis and delivered to late endosome or lysosomes where
a) Capsid proteins are proteolytically processed and lost generating infectious subviral particles
b) processing can occur either outside cells during passage through the gut or following endocytosis as above
What is the 2nd step of the rotavirus replication cycle?
Following penetration, enzymes within the core begin synthesizing mRNAs
a) Transcription is asymmetric (only individual (+) strand mRNAs (10-12) are made). These are extruded through the vertices of the capsid structure. mRNAs are capped, but not polyadenylated
What is the 3rd step of the rotavirus replication cycle?
Some of the capped mRNAs are subsequently assembled into 'assortment complexes'
a) Capped (+) strand RNAs serve as templates for synthesis of the complementary (-) strands producing each of the double-strands RNA genome segments
What are the 4th and 5th steps of the rotavirus replication cycle?
4th: Assembly of retovirus particles occurs entirely within the cytoplasm in viroplasms and form distinct cytoplasmis inclusion bodies
5th: Progeny virus is subsequently release by host cell lysis
What is the major cause of foodbourne epidemic acute gastroenteritis in older children and adults?
Noroviruses (Caiciviridae) (aka Norwalk or Norwalk-like viruses)
What is the genome of Noroviruses?
Nonenveloped, non-segmented (+) strand RNA viruses
Note that the replication scheme of caliciviruses has not been determined but may be similar to picornaviruses
Again, rotaviruses cause diarrheal disease primarily in ______
the young (responsible for 35-50% of hospitalization for severe diarrhea during the first 2 yrs of life)
_____ are responsible for ~50% of community-based outbreaks of nonbacterial gastroenteritis in older (school-aged) children and adults
Noroviruses (known as 'winter vomiting disease')
Transmission of both rota- and noroviruses is primarily by the ______ route
fecal-oral (both are very stable in the environment)
Norovirus outbreaks are often linked to a single source. Name some.
Contaminated food (raw or steamed shellfish, cake frosting, and salads)
Contaminated water (Cruise ship outbreaks)
The clinical symptoms for both rota- and norovirus infections include:
Both rota- and noroviruses initially infect villus epithelium of the _________
a) Virus replication and cell lysis then causes loss of cells lining the small and large intestine, resulting in functional alterations in the small intestine villous epithelial cells
b) Glucose-coupled sodium transport is impaired, but adenylate cyclase and cAMP are not stimulated (thereore not like v. cholera mechanism)
What is most important for protection against reinfection by both rota- and noroviruses?
local (intestinal) immunity
Describe immunity to rotaviruses and noroviruses
AB to rotaviruses are obtained relatively early in life, but ABs to noroviruses are acquired gradually in childhood, and increase steadily over a person's lifetime
T or F. There are 4 major serotypes of rotaviruses that cuase most disease
T. making development of a vaccine practical even though there is potential for significant antigenic diversity through antigenic shift and drift
T or F. Norovirus immunity is not long lasting
T. Antigenic diversity is generated via antigenic drift, similar to other single-stranded RNA viruses
What rotavirus vaccines are available?
a) RotaTeq (pentavalent bovine-human reassortant viruses (serotypes G1-G4 and P8). Live, attenuated given PO at 2,4, and 6 mos.
b) Rotarix (human-derived monovalent (G1, P8). Live, attenuated given PO in two doses starting at 6 weeks of age
**There are no approved norovirus vaccines**
What are the most important preventative measures for norovirus?
-effective disinfection of surfaces
-proper food prep
What is the genome of Astroviruses?
Non-enveloped, icosahedral, single-stranded (+) sense RNA viruses with a characteristic star-like appearance on EM
___ are second to rotaviruses as the most common cause of childhood diarrhea in children and infants under 1 yo
Describe the diversity of astroviruses
There are 8 serotypes that all cause gastroenteritis, predominantly diarrhea, mainly in children under 5 yo
80% of children 5-10 have Abs to Astroviruses
How are astroviruses spread?
How does astrovirus infection present?
Illness is self-limiting, of short-duration and has a peak incidence in WINTER (no vaccine available)
What is the genome of Enterovirsues (Picornaviridae)?
Small, icosehedral nonenveloped (+) sense RNA viruses
What are the human enteroviruses?
Poliovirus (causes flaccid paralysis (poliomyelitis)
Coxsackievirus (A and B)