Rotavirus, Norovirus, and Rabies Virus

family reoviridae is divided into ___ genera, and which genera are able to infect humans?

15, orthoreovirus, rotavirus, coltivirus, orbivirus

what are the genera of the reoviridae divided into?

spinareovirinae- viruses with large spikes at the 12 vertices on the particle (orthoreovirus)

sedoreovirinae- appear more smooth, lacking the large surface projections (rotavirus)

fast facts about reoviridae

non-enveloped, triple (double) capsid, icosahedral, virion, 60-80nm, dsRNA genome, 10-12 segments, very durable virus

what virus is also segmented, and why do we care?

reoviridae and influenzae

segments make it easier for antigenic shift

fast facts about orthoreovirus

widespread and very common virus, sewage and water, 75% of adults have antibodies, useful for research

what genera of the reoviridae family are arboviruses?

coltivirus and orbivirus

fast facts of rotavirus

major (if not #1) cause of infant death in underdeveloped countries, causes infantile diarrhea, infections in adult humans and animals are also common, extremely resistant capsid

have typical reovirus structure

replication: uncoating requires harsh treatment, proteases/acid pH, ISVP

ISVP

infectious sub viral particle, major distinction between strains of rotavirus (has ISVP) and adenovirus/coronaviruses (does not have) causing diarrhea

what are the hosts for rotavirus?

wide host range, cross-species infections can occur in experimental inoculations (not clear if they occur in nature), newborns often exhibit subclinical infection (presence of maternal antibody)

how is rotavirus transmitted?

fecal-oral route

what are the antigenic properties of rotavirus?

classified into 8 groups (A-H) based on antigenic epitopes and sequence of the internal structural protein VP6

outer capsid proteins VP4 and VP7 used to define sub-groups

how does rotavirus infect?

survives in GI tract, infects columnar epithelial cells of small intestine, blocks water absorption, causes watery diarrhea

loss of water and electrolytes may lead to dehydration, acidosis, shock, and death

what are the clinical manifestations of rotavirus?

gastroenteritis, 48-hour incubation, vomiting, diarrhea, fever, and dehydration, no blood or fecal leucocytes in stool sample

how can rotavirus be diagnosed in the lab?

direct detection of virus in stool

ELISA- sandwich assays

RT-PCR- most sensitive

serology- 4 fold increase in titer, most people are seropositive, by age of 3 90% of children have serum antibodies to one or more types, rotavirus antibodies are maintained in adults, information can be obtained in clinically relevant time period

rotavirus group A

single most important cause (viral or bacterial) of endemic severe diarrheal illness in infants and young children worldwide (in cooler months in temperate climates)

enteric adenovirus

second most important viral agent of endemic diarrheal illness of infants and young children worldwide

noroviruses

important cause of outbreaks of vomiting and diarrheal illness in older children and adults in families, communities, and institutions, frequently associated with ingestion of food

rotavirus is the most important worldwide cause of ____ in young children

~___ deaths occur in developing countries

developed countries have a high _____ rate but a low ____ rate

usually predominate during the ____ season

gastroenteritis, 1 million, morbidity, mortality, winter

how is rotavirus treated?

management, replacement of fluids, restoration of electrolyte balance, intravenously or orally

rotarix

rotavirus vaccine, oral live virus, human serotypes G1-G4 and G9, attenuated human strain, 2 doses

rotaTeq

oral live vaccine, 5 human serotypes G1-G4 and P1, bovine rotavirus, 3 doses

rotashield

withdrawn from the US, intussusception side effect, still used in developing world

fast facts of calicivirus

+sense, single stranded RNA, not segmented, 13 species, divided among 11 genera, cause viral gastroenteritis in human

which caliciviruses are of medical importance for humans?

norovirus (previously called norwalk virus), noro-like virus

noroviruses

also called small round gastroenteritis viruses, causative agent of winter vomiting disease

fast facts about norovirus

slightly larger than picornaviruses, 27-40nm, 3 genogroups are associated with human gastroenteritis designated GI, GII, GIV

what is the mode of transmission of norovirus?

fecal-oral, narrow tissue range

cellular receptors- histocompatibility blood group antigens that are expressed on the mucosal epithelia of the digestive tract

how does the norovirus infect?

disrupt the function of (or lyse) brush border epithelial cells in the intestine

blocking of proper absorption of water and nutrients causing gastroenteritis

what are the clinical findings of noroviruses

winter vomiting disease, symptoms develop after a 1-3 day incubation period, normally lasts 2-3 days, low grade fever, vomiting, diarrhea (not bloody), and headache

mild and self-limiting disease, immunity is short-lived

a common source of travelers diarrhea

what causes norovirus outbreaks?

single source transmission (food, water, shellfish)

primary cause of food and water borne viral gastroenteritis in the USA

primary cause of food borne gastroenteritis outbreaks in the USA

highly contagious- regularly causes outbreaks in institutions, hotels, and cruise ships

how can norovirus be diagnosed in the lab?

RT-PCR is fast and becoming common, virus can be directly detected in stool by antibody, IEM

IEM

immunoelectron microscopy

mix anti-viral antibody with stool sample and allow antibody:viral complexes to form, perform a negative stain and examine under EM (fast, only takes a few hours), serology is also used especially in outbreaks

how can norovirus be treated?

treat gastric symptoms and prevent dehydration, reduce severity of outbreaks by cleaning and enforced hygiene, no effective antivirals are available

is there a vaccine for norovirus?

no

what are the important members of the rhabdoviridae family?

rabies virus (hydrophobia, encephalitis, zoonotic, not a fast growing virus), vesicular stomatitis virus (prototype virus of this family)

rabies

acute infection of the central nervous system, fatal, transmitted to humans from the bite of a rabid animal, major public health problem because it is widespread among animal reservoirs

fast facts of rabiesvirus

enveloped, bullet-shaped virions, 75×180nm, helical nucleocapsid, - sense, single stranded RNA, virions contain an RNA dependent RNA polymerase

what are the hosts of rabiesvirus?

wide host range, all warm blooded animals including humans can be infected, distributed in infected animal (especially in the nervous system) saliva, urine, lymph, milk, and blood

what are the antigenic properties of rabiesvirus?

single serotype, strain differences among viruses isolated from different species

how is rabiesvirus spread and what is its pathways once it infects?

animal bite, virus replicates at infection site (can last days to months), neurotropic virus, travels to dorsal root ganglia and spinal cord by retrograde axoplasmic transport, infects brain, descends to glands and skin

where can rabiesvirus be found after infection?

brain to afferent neurons

skin, salivary glands, retina, cornea, nasal mucosa, adrenal medulla

replication in salivary glands and virus shedding in saliva

encephalitis and neuronal degeneration

once clinical symptoms appear death is almost certain

where is rabiesvirus endemic?

everywhere except australia and UK

rabiesvirus in the US

one death in 2004 was from an organ transplant, racoons are most commonly reported rabid animal, and bat bites can go untreated

what are the clinical findings of rabiesvirus?

acute, fulminant, fatal encephalitis, incubation period in humans is typically 1-3 months, usually shorter in children than in adults

clinical spectrum can be divided into 3 phases… short prodromal phase, acute neurologic phase, coma

clinical findings of short prodromal phase of rabies

nonspecific symptoms- malaise, anorexia, headache, photophobia, nausea, vomiting, sore throat, and fever

abnormal sensation around the wound site

clinical findings of acute neurological phase of rabies

nervous system dysfunction- nervousness, apprehension, hallucinations, and bizarre behavior

pupillary dilation, increased salivation, perspiration

hydrophobia and aerophobia

clinical findings of coma phase of rabies

convulsive seizures or coma and death

how can rabiesvirus be diagnosed in the lab?

no test to diagnose rabies infections in humans before the onset of clinical symptoms

rabies can be diagnosed from euthanized animals by direct fluorescent antibody testing of brain tissue

definitive pathologic diagnosis- negri bodies in the brain or the spinal cord

negri bodies

sharply demarcated spherical structures that have a distinctive internal structure with basophilic granules in an eosinophilic matrix

how can rabiesvirus be prevented?

canine vaccination programs, postexposure prophylaxis, washing wound with soap, passive antibody injection at wound site

is there a vaccine for rabiesvirus?

yes- series of shot in the arm, RIGG in glute or wound

HRIG (human) in USA or ERIG (animal) in developing countries

This virus is the most important cause of gastroenteritis in infants and young children. It causes infections that are often severe and may be life

threatening, especially in infants.

A. Escherichia coli

B. Norwalk virus

C. Rotavirus, group A

D. Rabies

E. Vibrio cholerae

C. Rotavirus, group A