Reoviridae

Overviewreoviridae_clip_image002

Viruses in the Reoviridae family can be found all over the world. From contaminated water supplies to small ticks, these viruses have multiple routes of transmission


10 ThingsReoviridae_virion

  1. Reovirus refers to “respiratory enteric orphan virus.” “Respiratory enteric” refers to viral tropism for respiratory and intestinal cells. “Orphan” refers to the fact that some viruses have no disease associations.
  2. Viruses in the Reoviridae family can be transmitted fecal-orally (though CTFV is an ARBO virus).
  3. Two subfamilies exist. Sedoreovirinae, containing the genera Orbivirus and Rotavirus, and Sprinareovirinae, containing the genera Coltivirus (CTFV) and Orthoreovirus.
  4. Reoviruses are double-stranded RNA viruses that infect vertebrates, insects, plants, and fungi. They have linear genomes that contain 10 – 12 segments. They are not enveloped, and their capsids (which have 2-3 layers) are icosahedral shaped.
  5. Reoviruses are believed to be the only dsRNA viruses that can infect humans.
  6. Rotavirus and Colorado Tick Fever Virus are the most pathogenic viruses in humans. Rotavirus causes severe gastrointestinal disease, especially in children. Colorado Tick Fever Virus is an ARBO virus that causes neurological disease in humans.
  7. In mouse models, RNAse L has been identified as a key component in identifying and destroying dsRNa.
  8. No targeted antiviral treatments are currently available against Reoviruses. Diarrhea can lead to severe dehydration, which can sometimes be treated with IV fluids or Oral Rehydration Therapy.
  9. There are two licensed vaccines against rotavirus in the U.S. Rotateq – 3 doses at 2, 4, and 6 months of age – and Rotarix – 2 doses at 2 and 4 months of age. Both vaccines are administered orally.
  10. The virus enters target cells via the “JAM-A” protein and integrin proteins. Binding triggers clathrin-mediated endocytosis.

Reo History 

  • 1943 – Jacob Light and Horace Hodes isolate an infectious, filtrable agent associated with diarrheal disease
  • 1944 – Colorado Tick Fever Virus is first isolated from human blood
  • 1973 – Bishop, Davidson, Holmes, and Ruck find Rotavirus in the cytoplasm of duodenal epithelial cells and feces
  • 1974 – Thomas Flewett proposes the name rotavirus after noticing a wheel-like resemblence under a microscope
  • 1981 – Trypsin, a protease involved in digestion, is associated with rotaviral replication
  • 1998 – Rotashield, the first vaccine against rotavirus, is licensed and recommended
  • 1999 – Wyeth Pharmaceuticals withdraw Rotashield after alegations are made associating the vaccine with intussusception
  • 2006 – Rotateq, a new vaccine against rotavirus, becomes availablerotaqet
  • 2008 – Rotarix, another vaccine against rotavirus, becomes available.
  • 2015 – Bharat Biotech announces a $1 rotavirus vaccine (Rotavac) to be made available in India

Replication

rotavirus_cycleOrthoreoviruses are believed to undergo reassortment if cells become co-infected with two compatable strains of orthoreoviruses. This is similar to the antigenic shift that influenza undergoes. Replication of reoviruses occurs in the cytoplasm, and reoviruses package an RNA dependent RNA polymerase into their virion. Moreover, replication and transcription occur in partially uncoated virions. This may be a viral mechanism to avoid detection by TLR receptors of the innate immune system that detect dsRNA.

Reassortment

Having multiple reading frames per transcript increases the diversity of protein products the virus can synthesize.

Leaky Scanning

Some reoviral genomes produce mRNA transcripts that undergo leaky scanning. In leaky scanning, the ribosome can skip an upstream start codon and continue scanning the transcript for a subsequent start codon. In this manner, start codons may be in different frames, generating a mechanism for differential gene expression.

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