Virion Genome Genes and proteins Viruses and hosts Diseases Distinctive characteristics 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). Togaviruses - Togaviridae

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 Fig Alphavirus genome RNA.

Genes and proteins

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

Genes and proteins Fig A model for the temporal regulation of minus and plus-strand RNA synthesis.

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 Fig Processing and modification of Sindbis virus structural 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 Fig Alphavirus expression vectors.

Key Terms  Antigenome  Apoptosis  Arthropod-borne viruses   -galactosidase  Chloramphenicol acetyltransferase  Cryoelectron microscopy  Cytopathic  Encephalitis  Furin protease  Green fluorescent protein  Heparan sulfate  Hippocampus  Interferon  Laminin receptor  Methyltransferase  Packaging signal  Palmitoylation  Persistent infection  Polyprotein  Receptor-mediated endocytosis  Replicon  Reporter gene  RNA helicase  Signal peptidase  Subgenomic RNAs