Evolution of vesicular stomatitis virus in athymic nude mice: mutations associated with natural killer cell selection.
BHK-21 cells readily produce tumours in athymic nude mice, but BHK-21 cells persistently infected with wild-type vesicular stomatitis virus (VSV) do not. However, rare persistently infected virus-shedding tumours (VSV-P tumour cells) were independently derived by in vivo selection on three different occasions. Cloned viruses isolated from each of these (VSV-P virus mutants) carried mutations determining the VSV-P phenotype because they all allowed growth of virus-shedding tumours in nude mice when they were used to persistently infect normal (unselected) BHK-21 cells. Treatment of nude mice with anti-asialo-GM1 allowed BHK cells persistently infected with wild-type VSV to form tumours, and BHK cells persistently infected with VSV-P were resistant to natural killer (NK) cells in vitro; this implicates NK cells in the in vivo rejection of persistently infected tumours and in the selection of the VSV-P variant. In this paper, we have sequenced the glycoprotein (G protein), matrix (M) and non-structural (NS) proteins of three independently derived VSV-P type mutants to find mutations associated with in vivo passage of persistently infected nude mouse tumours and with resistance to NK cells. We found extensive mutation in the G protein of VSV-P but relatively few mutations in the M and NS proteins. This suggests but does not prove a role for the G protein in NK cell killing of infected cells.
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D006224:Cricetinae; D005814:Genes, Viral; D007111:Immunity, Cellular; D007694:Killer Cells, Natural / Q000276:immunology*; D008562:Membrane Glycoproteins; D008565:Membrane Proteins / Q000276:immunology; D051379:Mice; D008819:Mice, Nude / Q000276:immunology / Q000382:microbiology*; D009154:Mutation; D009374:Neoplasms, Experimental / Q000235:genetics / Q000382:microbiology; D012641:Selection, Genetic; D014721:Vesicular stomatitis Indiana virus / Q000235:genetics* / Q000276:immunology; D014759:Viral Envelope Proteins; D014763:Viral Matrix Proteins; D014764:Viral Proteins / Q000235:genetics*
C028391:G protein, vesicular stomatitis virus; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D014759:Viral Envelope Proteins; D014763:Viral Matrix Proteins; D014764:Viral Proteins