Togaviruses -togaviridae

Togaviruses -Togaviridae

Togaviruses -Togaviridae

• Virion

• Spherical enveloped particle with a fringe of projections.
• Diameter 70 nm.
• Nucleocapsid has icosahedral symmetry (T = 4).
• Envelope glycoproteins also arranged with icosahedral symmetry, T = 4.

Togaviruses - Togaviridae

• Genome

• Linear ss RNA, positive sense.
• Alphaviruses: 11 Kb; rubella virus: 9 Kb.
• 5 end is capped and methylated.
• 3 end has a 70-nt poly(A) tail.

Togaviruses - Togaviridae

• Genes and proteins

• Four nonstructural proteins (for viral RNA synthesis) translated directly from genome RNA.
• Five structural proteins (one capsid protein, three envelope proteins, a small hydrophobic protein) translated from a subgenomic mRNA.

Togaviruses - Togaviridae

• Viruses and hosts

• Two genera: Alphavirus (27 members) and Rubivirus (rubella virus).
• Alphaviruses (Sindbis, Semliki Forest, Ross River) infect birds and mammals.
• Most alphaviruses are transmitted by mosquitoes.

Togaviruses - Togaviridae

• Diseases

• Symptoms include fever, rash, arthritis, and encephalitis; can be fatal.
• Rubella infection (German measles) can lead to fetal abnormalities.

Togaviruses - Togaviridae

• Distinctive characteristics

• A subgenomic mRNA codes for virion structural proteins.
• Structural proteins are synthesized as a polyprotein that undergoes cleavage and membrane association.
• RNA replication is associated with cytoplasmic membranes.
• Alphaviruses have the unusual ability to replicate in both invertebrate and vertebrate hosts.
• Lipid envelope derived from the plasma membrane (vertebrate cells) or internal membranes (insect cells).

Virion

• Most togaviruses are arthropod borne, transmitted between vertebrate hosts by mosquitoes

Virion

• Togavirus virions contain a nucleocapsid with icosahedral symmetry wrapped in an envelope of the same symmetry

Virion

• Togaviruses enter cells by low pH-induced fusion inside endosome vesicles

• Nonstructural proteins are made as a polyprotein that is cleaved by a viral protease

Genes and proteins

Genes and proteins

• Partly cleaved nonstructural proteins catalyze synthesis of full-length antigenome RNA

Genes and proteins

Genes and proteins

• Replication and transcription: synthesis of genome and subgenomic RNAs

• Structural proteins are cleaved during translation and directed to different cellular locations

Genes and proteins

Genes and proteins

• Assembly of virions and egress at the plasma membrane

• Effects of mutations in viral proteins on cytopathic effects and on pathogenesis

• nsP2 mutation decreases viral RNA systhesis
• Do not cause cytopathic effect

Genes and proteins

• Alphaviruses have been modified to serve as vectors for the expression of heterologous proteins

• Alphavirus vectors have multiple potential uses

• Express proteins of unrelated viruses
• Express proteins toxic to insects

Genes and proteins

Key Terms

• Antigenome

• Apoptosis

• Arthropod-borne viruses

• -galactosidase

• Chloramphenicol acetyltransferase

• Cryoelectron microscopy

• Cytopathic

• Encephalitis

• Furin protease

• Green fluorescent protein

• Heparan sulfate

• Hippocampus

• Interferon