REOVIRUS -ROTAVIRUS

R.Varidianto Yudo T., dr.,MKes.Lab. Mikrobiologi

Fakultas Kedokteran Universitas Hang Tuah

CHARACTERISTIC• Virion: Icosahedral, 60–80 nm in

diameter, double capsid shell • Genome: Double-stranded RNA,

linear, segmented (10–12 segments); total genome size 16–27 kbp 

• Proteins: Nine structural proteins; core contains several enzymes. Main enzym is RNA-dependent RNA polymerase 

• Envelope: None (transient pseudoenvelope is present during rotavirus particle morphogenesis) 

Gel diagram showing the 11 segments of the genome. The structural (VP) and nonstructural (NSP) proteins encoded by these

segments are indicated.

Surface representation of the rotavirus structure from cryo-electron microscopic analysis. The two outer layer proteins are VP4, which

forms the spikes, and VP7, which forms the capsid layer

Cut-away view showing the triple-layered organization of the virion, with the intermediate VP6 layer and the innermost VP2 layer

indicated. The enzymes required for endogenous transcription (VP1) and capping (VP3) are attached as heterodimeric complexes to the inner surface of the VP2 layer. Proposed organization of the

double-stranded RNA genome inside the VP2 layer along with transcription enzyme complexes (VP1/3) depicted as balls.

Exit of transcripts from the channels at the 5-fold vertices of actively transcribing double-layered particles. Close-up view of one

of the exit channels.

REPLICATION• Reoviruses attach to the cell surface at the

site of the - adrenergic receptor. • Only the outer shell of the virus is removed,

and a core-associated RNA transcriptase is activated.

• This transcriptase transcribes mRNA molecules from the minus strand of each genome double-stranded RNA segment (10 or 11 segments) contained in the intact core.

• Reovirus cores contain all enzymes necessary for transcribing, capping, and extruding the mRNAs from the core, leaving the double-stranded RNA genome segments inside.

• Once extruded from the core, the mRNAs are translated into primary gene products.

• Some of the full-length transcripts are encapsidated to form immature virus particles.

• A viral replicase is responsible for synthesizing negative-sense strands to form the double-stranded genome segments.

• This replication to form progeny double-stranded RNA occurs in partially completed core structures.

• Rotavirus morphogenesis involves budding of single-shelled particles into the rough endoplasmic reticulum.

• The "pseudoenvelopes" so acquired are then removed and the outer capsids are added

• The virus is released from the cytoplasm by lysis of the cell, not by budding.

CLASSIFICATION• Rotaviruses have been classified into

five species (A–E), plus two tentative species (F and G), based on antigenic epitopes on the internal structural protein VP6.

• These can be detected by immunofluorescence, ELISA, and immune electron microscopy (IEM).

• Group A rotaviruses are the most frequent human pathogens.

PATHOGENESIS• Rotaviruses infect cells in the villi of

the small intestine (gastric and colonic mucosa are spared).

• They multiply in the cytoplasm of enterocytes and damage their transport mechanisms.

• One of the rotavirus-encoded proteins, NSP4, is a viral enterotoxin and induces secretion by triggering a signal transduction pathway.

• Damaged cells may slough into the lumen of the intestine and release large quantities of virus, which appear in the stool (up to 1010 particles per gram of feces).

• Viral excretion usually lasts 2–12 days in otherwise healthy patients but may be prolonged in those with poor nutrition.

• Diarrhea caused by rotaviruses may be due to impaired sodium and glucose absorption as damaged cells on villi are replaced by nonabsorbing immature crypt cells.

• It may take 3–8 weeks for normal function to be restored.

EPIDEMIOLOGY & IMMUNITY • Rotaviruses are the single most important

worldwide cause of gastroenteritis in young children. Developed countries have a high morbidity rate but a low mortality rate.

• Typically, up to 50% of cases of acute gastroenteritis of hospitalized children throughout the world are caused by rotaviruses.

• Rotavirus infections usually predominate during the winter season. Transmission appears to be by the fecal-oral route. Nosocomial infections are frequent.

• Rotaviruses are ubiquitous. By age 3 years, 90% of children have serum antibodies to one or more types. This high prevalence of rotavirus antibodies is maintained in adults, suggesting subclinical reinfections by the virus.

• Rotavirus reinfections are common; it has been shown that young children can suffer up to five reinfections by 2 years of age.

• Asymptomatic infections are more common with successive reinfections.

• Local immune factors, such as secretory IgA or interferon, may be important in protection against rotavirus infection.

• Asymptomatic infections are common in infants before age 6 months, the time during which protective maternal antibody acquired passively by newborns should be present.

• Such neonatal infection does not prevent reinfection, but it does protect against the development of severe disease during reinfection.

TREATMENT & CONTROL• Treatment of gastroenteritis is supportive, to

correct the loss of water and electrolytes that may lead to dehydration, acidosis, shock, and death. Management consists of replacement of fluids and restoration of electrolyte balance either intravenously or orally, as feasible. The infrequent mortality from infantile diarrhea in developed countries is due to routine use of effective replacement therapy.

• In view of the fecal-oral route of transmission, wastewater treatment and sanitation are significant control measures.

• An oral bovine-based rotavirus vaccine was licensed in the United States. A safe and effective vaccine remains the best hope for reducing the worldwide burden of rotavirus disease.