A cell-free stock of simian-human immunodeficiency virus that causes AIDS in pig-tailed macaques has a limited number of amino acid substitutions in both SIVmac and HIV-1 regions of the genome and has altered cytotropism

被引:50
作者
Stephens, EB
Mukherjee, S
Sahni, M
Zhuge, W
Raghavan, R
Singh, DK
Leung, K
Atkinson, B
Li, Z
Joag, SV
Liu, ZQ
Narayan, O
机构
[1] Dept. Microbiol., Molec. Genet., I., Marion Merell Dow Lab. Viral P., University of Kansas Medical Center, Kansas City
关键词
D O I
10.1006/viro.1997.8534
中图分类号
Q93 [微生物学];
学科分类号
071005 ; 100705 ;
摘要
We have examined both the sequence changes in the LTR, gag, vif, vpr, vpx, tat, rev, vpu, env, and nef genes and the cell tropism of a cell-free stock of chimeric simian-human immunodeficiency virus (SHIV) isolated from the cerebrospinal fluid of a pig-tailed macaque (PNb) that developed AIDS. This virus (SHIVKU-1) is highly pathogenic when inoculated into other macaques. DNA sequence analysis of PCR-amplified products revealed a total of 5 nucleotide changes in the LTR while vif had 2 consensus amino acid changes. The gag, vif, and vpx had no consensus amino acid substitutions, whereas vpr had 1 consensus substitution. The tat and rev genes of the HXB2 region of SHIVKU-1 had 2 and 1 consensus amino acid changes, respectively. The vpu gene of the HXB2 region of SHIV, which originally had an ACG codon al the beginning of the gene, reverted to an initiation ATG codon and in addition contained a consensus amino acid substitution al position 69 of this protein. As expected, the majority of the nucleotide substitutions were found in the env and nef genes. Thirteen and 5 amino acid changes were predicted for the corresponding Env and Nef proteins, respectively. In addition, one-third of the env gene clones isolated from the SHIVKU-1 stock had a 5-amino-acid deletion in the V4 region. Using three independent assays, we determined that the changes in the SHIVLU-1 were associated with an increase in the efficiency of replication in macrophages. The strikingly few consensus changes in the virus suggest that conversion of this virus to one capable of causing AIDS in pig-tailed macaques was associated with relatively few changes in the viral envelope and/or accessory genes. These results will provide the basis for the development of a pathogenic, molecular clone of SHIV capable of causing AIDS in pig-tailed macaques. (C) 1997 Academic Press.
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页码:313 / 321
页数:9
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