Significance of premature stop codons in env of simian immunodeficiency virus. NLM AIDSLINE Important note: Information in this article was accurate in 1990. The state of the art may have changed since the publication date.

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Significance of premature stop codons in env of simian immunodeficiency virus.

J Virol. 1989 Nov;63(11):4709-14. Unique Identifier : AIDSLINE MED/90012321
Kodama T; Wooley DP; Naidu YM; Kestler HW 3d; Daniel MD; Li Y; Desrosiers RC; New England Regional Primate Research Center, Harvard Medical; School, Southborough, Massachusetts 01772.


Abstract: The location of the translational termination codon for the transmembrane protein (TMP) varies in three infectious molecular clones of simian immunodeficiency virus from macaques (SIVmac). The SIVmac251 and SIVmac142 infectious clones have premature stop signals that differ in location by one codon; transfection of these DNAs into human HUT-78 cells yielded virus with a truncated TMP (28 to 30 kilodaltons [kDa]). The SIVmac239 infectious clone does not have a premature stop codon in its TMP-coding region. Transfection of HUT-78 cells with this clone initially yielded virus with a full-length TMP (41 kDa). At 20 to 30 days posttransfection, SIVmac239 virus with a 41-kDa TMP gradually disappeared coincident with the emergence of a virus with a 28-kDa TMP. Virus production dramatically increased in parallel with the emergence of a virus with a 28-kDa TMP. Sequence analysis of viral DNAs from these cultures showed that premature stop codons arising by point mutation were responsible for the change in size of the TMP with time. A similar selective pressure for truncated forms of TMP was observed when the SIVmac239 clone was transfected into human peripheral blood lymphocytes (PBL). In contrast, no such selective pressure was observed in macaque PBL. When the SIVmac239 clone was transfected into macaque PBL and the resultant virus was serially passaged in macaque PBL, the virus replicated very well and maintained a 41-kDa TMP for 80 days in culture. Macaque monkeys were infected with SIVmac239 having a 28-kDa TMP; virus subsequently recovered from T4-enriched lymphocytes of peripheral blood showed only the 41-kDa form of TMP. These results indicate that the natural form of TMP in SIVmac is the full-length 41-kDa TMP, just as in human immunodeficiency virus type 1. Viruses with truncated forms of TMP appear to result from mutation and selection during propagation in unnatural human cells.
Keywords: Amino Acid Sequence Animal Base Sequence Cell Line Cloning, Molecular Codon/*GENETICS DNA, Viral/GENETICS *Genes, Structural, Viral Human In Vitro Lymphocytes/MICROBIOLOGY Macaca Molecular Sequence Data Proviruses/GENETICS RNA, Messenger/*GENETICS Support, U.S. Gov't, P.H.S. SIV/*GENETICS/PHYSIOLOGY Transfection Viral Envelope Proteins/*GENETICS Virus Replication JOURNAL ARTICLEKWDaminoacidsequenceanimalbasesequencecelllinecloning,molecularcodon/KWDgeneticsdna,viral/geneticsKWDgenes,structural,viralhumaninvitrolymphocytes/microbiologymacacamolecularsequencedataproviruses/geneticsrna,messenger/KWDgeneticssupport,uKWDsKWDgov't,pKWDhKWDsKWDsiv/KWDgenetics/physiologytransfectionviralenvelopeproteins/KWDgeneticsvirusreplicationjournalarticle
900130
M9010412

Copyright © 1990 - National Library of Medicine. Reproduced under license with the National Library of Medicine, Bethesda, MD.

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