MicrobiologyBytes: Virology: Reoviruses Updated: September 11, 2007 Search

Reoviruses (incl. Rotaviruses)

MicrobiologyBytes: Latest Updates

Respiratory Enteric Orphan viruses, i.e. infect the human respiratory and intestinal tracts, usually without disease symptoms. First recognised in 1959 - and previously (wrongly) classified as echoviruses (Picornaviridae). There are >150 species in the family Reoviridae. They are a diverse group, infecting invertebrates, vertebrates and plants, but are unified by their most unique feature - the composition of their genome - d/s RNA:

Group III: dsRNA Viruses

Family

(Subfamily)

Genus

Type Species

Hosts

Reoviridae Orthoreovirus Mammalian orthoreovirus Vertebrates
Orbivirus Bluetongue virus Vertebrates
Rotavirus Rotavirus A Vertebrates
Coltivirus Colorado tick fever virus Vertebrates
Aquareovirus Golden shiner virus Vertebrates
Seadornavirus Banna virus Vertebrates
Cypovirus Cypovirus 1 Invertebrates
Idnoreovirus Idnoreovirus 1 Invertebrates
Fijivirus Fiji disease virus Plants
Phytoreovirus Wound tumor virus Plants
Oryzavirus Rice ragged stunt virus Plants
Mycoreovirus Mycoreovirus 1 Fungi

The dsRNA Viruses. Virus Res. 101: 3-13 (2004).

General Characteristics:

Host Range:

This family is ubiquitous in nature - infecting invertebrates, vertebrates and plants. Abs have been found in all species of mammals tested (except whales), implying wide cell tropism/ubiquitous receptor (see below).

Morphology:

All are similar: Non-enveloped, icosahedral capsids (T=13) composed of double protein shell: Outer shell ~80nm diameter; Inner shell ~60nm diameter. The various genera are serologically unrelated. Proteins:
Genus: Outer capsid: Core: Non-structural:
Reoviruses: σ-1, σ-3, μ-1c, λ-2 λ-1, λ-3, σ-2, μ-2 μ-NS, σ-NS
Orbiviruses: VP2, VP5, VP7 VP3;
VP1,VP4,VP6 (transcriptase complex)
NS1, NS2, NS3
Rotaviruses: VP4, VP7 VP2, VP6, VP1, VP3 NSP1, NSP2, NSP3, NSP4, NSP5, NSP5A

Cover

To view a negatively-stained electron micrograph of reovirus particles, click here. Reovirus particles are very stable environmentally (especially waterborne Rotaviruses!). To view a negatively-stained electron micrograph of Rotavirus particles, click here.

The Atomic Structure of the Bluetongue Virus Core. J.M.Grimes et al. Nature 395: 470 (1998).

Orthoreovirus Structure:

Reovirus structure

More detail is known about the structure/function relationships of the Reovirus capsid than most other viruses. Rotavirus particles have the appearance of a wheel with spokes radiating out from the inner capsid. Orbivirus particles appear smooth.

Genome:

Segmented, d/s RNA - 10 (Reo's) / 11 (Rota's) segments in three distinct size classes: These range in size from ~3.9kbp (L) - 1kbp (S). 30% of the RNA in the particles is in the form of small s/s oligonucleotides, synthesized internally by the viral polymerase - possibly abortive transcripts?

Replication:

Occurs in cytoplasm:
Reovirus replication

The receptor(s) are known to contain sialic acid (haemagglutination, broad cell tropism), but most have not been definitively identified.
Particles are internalized and partially uncoated in endolysosomes in the cytoplasm (resistant to protease digestion- if completely uncoated, virus would be destroyed).
Early transcription of the d/s RNA genome by viral polymerase occurs inside this sub-viral particle. The various genome segments are transcribed/translated at different frequencies - the main advantage of a segmented genome? (reassortment?)
RNA is transcribed conservatively - only (-)sense strands are used, resulting in synthesis of (+)sense mRNAs, which are capped inside the core - all this occurs without de novo protein synthesis.
mRNAs leave core and are translated in the cytoplasm.

Primary transcription (depending on factors inside the virus particle) results in capped transcripts which are not polyadenylated. At least 5 enzymatic activities are present in reovirus particles to carry out this process (not necessarily all separate peptides:

Activity:

Virus Protein:

Encoded by Genome Segment:

d/s RNA-dependent RNA polymerase (pol)

λ3

L3

RNA triphosphatase

μ2

M1

Guanyltransferase (cap)

λ2

L2

Methyltransferase

λ2

L2

Helicase (hel)

λ1

L1

Secondary transcription occurs later in infection in particles produced inside the infected cells and results in uncapped non-polyadenylated transcripts.

The genome is replicated in the cytoplasm in a conservative fashion (c.f. DNA replication) - an excess of (+)sense strands are produced which serve as late mRNAs and as template for (-)sense strand synthesis (i.e. each (-) strand leads to many (+) strands - not one-for-one as semi-conservative replication). The mechanism responsible for segregation of the various genome segments into developing particles is not known.

The bluetongue virus core: a nano-scale transcription machine. Virus Res. 101: 29-43 (2004).

At least some reoviruses require an activated Ras signaling pathway for replication. Since this is a characteristic of transfromed cells, it has been suggested that reoviruses might be used as oncolytic agents (Norman KL, et al PNAS USA 101: 11099-11104, 2004).

Particles assemble in the cytoplasm 6-7h after infection, forming inclusion bodies. Rotaviruses bud from the E.R. into internal spaces and are eventually released when the cell lyses.

Pathogenesis:

The majority of human Orthoreovirus infections involve the gastrointestinal & upper respiratory tracts & are asymptomatic, occasionally producing mild febrile illness, or very rarely, serious complications - orphan viruses. The majority of adults have Abs.

 

Bestsellers - Music - DVDs - Videos - Electronics
Search for ... (keywords):
Search for ... (keywords):

Bestsellers - Music - DVDs - Videos - Electronics

Rotaviruses

MicrobiologyBytes: Latest Updates

Infections cause endemic/epidemic gastroenteritis and infantile diarrhoea - second only to respiratory infections in infants <24 months - a major cause of death in the developing world:
Rotavirus incidence

Rotaviruses cause messy but generally self-limited infections, rare in adults (Abs) and trivial in consequence, but may kill infants unless properly treated - oral rehydration therapy (O.R.T.) with isotonic glucose/mineral salt solution keeps children alive (treats symptoms, not cause). Rotaviruses are also a major cause of mortality in young animals such as calves, piglets, etc - highly infectious. Studies published between 1986 and 1999 indicated that rotavirus causes ~22% of childhood diarrhea hospitalizations. From 2000 to 2004, this proportion increased to 39%. Application of this proportion to the World Health Organization estimates of diarrhea-related childhood deaths gives an estimated 611,000 rotavirus-related deaths (Parashar UD. Rotavirus and severe childhood diarrhea. Emerg Infect Dis. 2006 Feb;12: 304-306).

Rotavirus appear to cause diarrhea by triggering the intestinal nervous system to secrete more water (Lundgren O. et al. Role of the Enteric Nervous System in the Fluid and Electrolyte Secretion of Rotavirus Diarrhea. Science 287:491-495, 2000).
Blutt SE, Conner ME. Rotavirus: to the gut and beyond! Curr Opin Gastroenterol. 2007 23: 39-43
. Rotavirus antigens (antigenaemia), RNA, or infectious virus (viraemia) has been demonstrated in the serum and many extraintestinal tissues in all experimental animal models. Rotavirus antigens and RNA have been detected in the sera of children with rotavirus diarrhea. The tissues and cell types that support rotavirus replication outside the intestine and the consequences of extraintestinal reservoirs of infection are beginning to be examined. The impact of systemic rotavirus on disease burden remains to be determined.

Rotaviruses have three shells - an outer capsid, inner capsid and core which surrounds the 11 segments of double-stranded RNA. Two of the structural proteins, VP7 (the glycoprotein or G protein) and VP4 (the protease cleaved or P protein) make up the outer shell and define the serotype of the virus and are the major antigens involved in virus neutralization. Multistep entry of rotavirus into cells: a Versaillesque dance. Lopez S, Arias CF. Trends Microbiol. 2004, 12: 271-278.

A novel two-dose, oral vaccine called Rotarix has completed clinical trials and was licenced in Mexico in 2004. Discussions are ongoing about use of this vaccine in dozens of other countries, including India, Brazil, and Indonesia, but there are no plans to market it in the USA or Europe in the forseeable future, due to the preceived lower public health priority in countries with well developed healthcare systems.

Medscape: Update on Rotavirus Vaccines

Orbiviruses:

Similar in many respects to Orthoreoviruses. There are >130 serotypes of orbivirus which infect birds & mammals, including humans, causing a variety of haemorrhagic fevers, encephalitis & other conditions:
Properties: Orbivirus: Reovirus:
Acid sensitivity: Sensitive Resistant
Detergent sensitivity: Partial sensitivity Resistant
Tissue tropism: Haematopoetic & epithelial cells Intestinal tract
Transmission: Insect vector Faecal-oral

African Horse Sickness - fever followed by death within hours in >90% affected animals. Transmitted by midges, ticks. Vaccine available.

Bluetongue - Disease of sheep, also infects cattle, producing mild disease; severe economic pest - causes fetal loss. Transmitted by midges (Culicoides). An effective inactivated vaccine against BTV has not yet been commercially produced. Attenuated (‘live’) vaccines are used in S.Africa, the USA and Israel, and experimentally in the Mediterranean region, but provide little protection against heterologous challenge (i.e. of another serotype) although, if closely related, there may be protection against clinical disease and reduced viraemia. Multivalent live vaccines, if properly administered, prevent infection with all the relevant serotypes. The disadvantages of attenuated BTV vaccines are: - Risk of reassortment with wt viruses which potentially could give rise to new virulent strains.

Non-infectious subunit vaccines (recombinants and constructs) could overcome some of the problems of attenuated vaccines. Virus-like particle (VLP) vaccines have been successfully produced and have been shown in experimental studies to protect sheep from disease against a homologous challenge. Core-like particle (CLP) vaccines on the other hand are not serotype specific and show promise as a generic vaccine for the future.

Colorado Tick Fever - Tick transmitted disease endemic in USA. Acute febrile illness, usually without lasting consequences.



© MicrobiologyBytes 2007.