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)
What diseases does Caxsackievirus cause?
hand, foot, and mouth disease
inflammation of myo- and pericardium
What diseases do Echo- and Enteroviruses cause?
mild gastroenteritis (Hep A is also an 'enterovirus-like' picornavirus)
How are enteroviruses differentiated from rhinoviruses?
a) Acid stable
b) replication at 37C
T or F. Humans are the only known reservoir of enteroviruses
T. Spread fecal-oral
Describe the replication of Enteroviruses
There is a 7-14 day incubation period followed by initial replication in lymphoid tissue of the URT and the gut. Viremua results in infection of target organs including:
-spinal cord and brain
How do enteroviruses present?
asymptomatic infection is common
Note that besides polio there are no vaccines for other enteroviruses due to the large no. of serotypes
What is the genome of adenoviruses (Adenoviridae)?
large, nonenveloped, linear, dsDNA viruses
What serotypes of adenovirus are associated with gastroenteritis?
40 and 41
When does adenovirus gastroenteritis typically present?
generally in young children and infants with similar disease to rotavirus and astroviruses (most ppl have Abs by age 3)
How is adenovirus spread?
fecally-contaminated water (foodbourne transmission has not been documented)
H. Adults can get rotavirus, adeno, astro, its just more common in kids. Calicivirus is more common in adults
C. Kids CAN get C. diff
B, D, and F
Giardia is contracted from stream-like water (not likely)
Salmonella would present with BLOODY diarrhea (not likely)
E. Coli is more like to be inflammatory to0
Better access of supportive care and better identification of disease
Flu replicates in the nucleus and must undergo splicing
E. Norovirus= diarrhea and vomiting at the same time
Possible, but likely virus (Norovirus) based on timing
Norovirus can also be detected using a RT-PCR assay, but typically not done except for large outbreaks (like on cruise ships)
Need to know eneterovirus D68= caused gastrointestinal disease in infants lately
Virus can spread lonnngggg after disease
He is certainly at risk for HSV, CMV, Giardia lamblia, Campylobacter jejuni, Shigella spp, Salmonella spp, and C. difficile. I would also include Entamoeba histolytica, Dientamoeba fragilis, Blastocystis hominis.
Because of recent travel to Mexico, Yersinia spp, rotaviruses, and noroviruses are also in the differential.
In addition, I would include E. coli and Vibrio parahaemolyticus. He also could have diarrhea and wasting from HIV itself.
An exam of the stool showed many cysts of Giardia lamblia and Entamoeba histolytica. This diagnosis should be reported to the local public health department.