Lec 29 Viral GI Illnesses Flashcards
What is leading cause of childhood death?
diarrhea
What is most common viral cause of severe diarrhea in young children?
rotaviruses
Who gets rotaviruses?
children age 6 - 24 mos
What are signs of rotavirus infection?
- can be asymptomatic or severe dehydrating gastroenteritis
- fever
- vomiting
- watery diarrhea
- dehydration [more common in rotavirus than with other causes of infectious diarrhea]
Does rotavirus infect immuodeficient? HIV+?
- longer lasting more severe syndrome in immunodeficient
- not a common cause of diarrhea in HIV+ adults
Can reinfections of rotavirus occur?
- can occur but tend to be less severe
Whos gets rotavirus? when?
- almost all children infected before age 3
- adults infected when caring for infected infants
- seasonal infection –> peak in colder months, lower humidity
How is rotavirus transmitted?
- fecal oral route
- resistant to desiccation –> can survive 7 months in feces]
- shedding of large numbers of rotaviurs prior to, during and after infection
- short < 48 hr incubation time
- some evidence of maybe respiratory spread too
How is rotavirus diagnosed?
- ELISA or latex agglutination to detect viral antigen in stool
- RT-PCR of viral RNA
- electron micro of stool
- isolation in cell culture is possible
What are the 7 serogroups of rotavirus? where are they found?
groups A, B, C in animals and humans
groups D-G in animals
How are rotavirus serogroups determined?
reactivity of antibodies with VP6 [by ELISA]
How are the rotavirus serotypes determined?
- within each group based on reactivity of antibodies with VP7 [G antigen]
- also type based on reactivity of antibodies wtih VP4 [P antigen]
What are the common serotypes most important for human disease?
Group A serotypes G1, G2, G3
What is function of VP4 gene in rotavirus?
takes part in cell attachment
contains: hemagglutinin, neutralizing epitopes, P antigen
What is function of VP6 gene in rotavirus?
contains major group [A-G] antigen
What is function of VP7 gene in rotavirus?
contains neutralizing epitopes, G antigen
What is function of NSP4 gene in rotavirus?
codes for enterotoxin that aids in ER protein/assembly
What is structure of rotavirus?
- rota = wheel appearance by EM
- non-enveloped with 3 layer protein struct [double capsid + core]
- segmented [11 segments]
- double strand RNA
Where in cell does rotavirus replicated?
in cytoplasm
What proteins are in outer capsid? inner capid? core?
outer capsid = VP4 [P] + VP7 [G]
inner = VP6
core = VP2
What are important points of rotavirus replication cycle?
- replicated in cyto
- only uses viral enzymes
- dsRNA always associated with subviral particles
- subviral particles form and mature by budding through ER where they acquire outer capsid proteins
How do you replicate dsRNA?
- copied into mRNA by RNA dependent RNA pol
What is pathogenesis of rotavirus?
- diarrhea begins before signficiant damage to intestinal mucosa
- get viremia
- NSP4 enterotoxin plays important part in diarrhea
- replicated in small intestinal epithelial cells
- net secretion water and loss of ions
What distinguishes bacterial from rotavirus diarrhea?
rotavirus diarrhea has minimal intestinal inflammation in comparison
What is immune response to rotavirus?
- antibodies in lumen of small intestine most important for protection
- T cell may play role
- first infection indunce homotypic immunity [anti-VP7 and VP4]
- prior infection reduces likelihoood and severity of new infections = cross-protective immunity
What are vaccines for rotavirus?
- jennerian vaccines: animal strains attenuated in humans as live vaccines
- reassortment vaccines
- attenuated human strain
What is mech of RotaTeq?
- live, pentavalent [G1, G2, G3, G4, G6
- human-bovine reassortment vaccine for rotavirus
- for infants younger than 32 wks
- not administered to infants with immunodeficiency
Mech of rotarix?
monovalent [G1P(8)] vaccine from most common human rotavirus strain
- attenuated
- provides partial cross-protection against other serotypes
Mech of RotaShield? bad side effect?
- oral tetravalent human-rhesus rotavirus reassortment
- link to intussusception so withdraw from market
What is the most common cause of outbreaks of nonbacterial gastroenteritis?
norovirus
What are the two types of human caliciviurses?
- noroviruses
- sapporo-like viruses
What are the bio properties of norovirus?
- difficult to propagate in culture
- non-enveloped
- sing strand
- pos sense
- linear RNA
Where does norovirus replicate in cell?
in cytoplasm
How is norovirus spread?
- fecal-oral transmision -> person to person, or from contaminated surface, fomites, airborne droplets]
What is incubation period of norovirus? how long does it last?
- incubation 1-2 days
- illness 1-2 days
How long does viral shedding last in norovirus?
viral shedding can last 2 wks
Who gets norovirus?
older children and adults
What are symptoms of norovirus?
mild: fever, watery diarrhea
sever: fever, vomiting, headache, constitutional symptoms
adults –> diarrhea
children –> vomitting
can be asymptomatic carrier
What is immune response to norovirus?
- infection induces antibodies that prevent illness following administration of homologous virus
What is secretor negative phenotype?
- mutations in FUT2 gene encoding gene for H antigen found on epithelial cell surface –> no NV binding, no virus shedding
- resistant to norovirus
How is norovirus diagnosed?
- not usually made in clinical setting
- identify by EM, RT-PCR, ELISA
