p6gag of human and simian immunodeficiency viruses is tolerant to small in-frame deletions downstream of the late domain.
Short, unique, in-frame deletions were consistently detected within p6gag sequences obtained over time from three of eight HIV-1-infected long-term nonprogressors (Alexander, L., Weiskopf, E., Greenough, T.C., Gaddis, N.C., Auerbach, M.R., Malim, M.H., O'Brien, S.J., Walker, B.D., Sullivan, J.L., Desrosiers, R.C., 2000. Unusual polymorphisms in Human Immunodeficiency Virus Type 1 associated with nonprogressive infection. J. Virol. 74, 4361-4376). Using PCR mutagenesis, we created 11 mutant forms of SIV239 and 8 mutant forms of HIV-1 NL4-3 with serial 2 amino acid deletions within p6gag downstream of the PTAP late domain. Nine of the 11 SIV239 mutants assembled and released virion particles similar to wild-type, displayed wild-type infectivity, and replicated similar to wild-type SIV239 in cultured cells. Two of the 11 SIV239 mutants, both involving D at position 21, were grossly defective for intracellular gag accumulation and did not replicate detectably in cultured cells. Similar to the 9 SIV239 mutants, 7 of the 8 HIV-1 mutants replicated well in cultured cells. Only the mutant deleted of ES at positions 19 and 20, immediately adjacent to the PTAP sequence, was markedly impaired in its replicative capacity. These results demonstrate an overall high tolerance of SIV and HIV to two amino acid deletions within p6gag downstream of the late domain.
Pikora
Cheryl A
CA
New England Primate Research Center, Harvard Medical School, One Pine Hill Drive, Southborough, MA 01772, USA.
Wittish
Christine
C
Desrosiers
Ronald C
RC
D000595:Amino Acid Sequence; D000818:Animals; D002460:Cell Line; D002478:Cells, Cultured; D015683:Gene Products, gag / Q000096:biosynthesis / Q000235:genetics* / Q000502:physiology; D016655:HIV Core Protein p24 / Q000096:biosynthesis; D015497:HIV-1 / Q000235:genetics* / Q000502:physiology*; D006801:Humans; D008214:Lymphocytes / Q000821:virology; D008253:Macaca mulatta; D008969:Molecular Sequence Data; D016296:Mutagenesis; D016133:Polymerase Chain Reaction; D017384:Sequence Deletion; D015302:Simian Immunodeficiency Virus / Q000235:genetics* / Q000502:physiology*; D019065:Virus Assembly; D014779:Virus Replication; D054301:gag Gene Products, Human Immunodeficiency Virus
C066594:Gag protein p27, Simian immunodeficiency virus; D015683:Gene Products, gag; D016655:HIV Core Protein p24; D054301:gag Gene Products, Human Immunodeficiency Virus; C083002:p6 gag protein, Human immunodeficiency virus 1