Construction and infection of a new simian/human immunodeficiency chimeric virus (SHIV) containing the integrase gene of the human immunodeficiency virus type 1 genome and analysis of its adaptation to monkey cells.
Expanding the HIV-1-derived regions in the SHIV genome may help to clarify the viral restriction factors determining the host range. In this study, we constructed a new SHIV having the reverse transcriptase and integrase-encoding regions of HIV-1 in addition to the 3' half genomic region of HIV-1. This SHIV, termed SHIVrti/3rn, could replicate in a monkey CD4+ T cell line, HSC-F, although its replication in monkey PBMCs was very weak. After SHIVrti/3rn was passaged in HSC-F cells for 26weeks, it gradually began to replicate in monkey PBMCs. This monkey-cell-adapted virus, termed SHIVrti/3rnP, could replicate in rhesus macaques. The whole genome of SHIVrti/3rnP was sequenced and was found to differ from SHIVrti/3rn at eleven positions. We constructed a series of mutants having some or all of these mutations and investigated their replication kinetics. The mutational analysis revealed that all of the mutations, but mainly the mutations in env, were responsible for the adaptation in HSC-F cells and were enough to replicate in rhesus PBMCs. Of all the SHIVs reported so far that can infect rhesus monkeys in vivo, SHIVrti/3rnP is the one that is genetically the closest to HIV-1.
Akiyama
Hisashi
H
Laboratory of Primate Model, Experimental Research Center for Infectious Diseases, Institute for Virus Research, Kyoto University, 53 Shogoin-Kawaracho, Kyoto 606-8507, Japan.
Ishimatsu
Misa
M
Miura
Tomoyuki
T
Hayami
Masanori
M
Ido
Eiji
E
D000220:Adaptation, Biological; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000821:virology; D002460:Cell Line; D016679:Genome, Viral; D015483:HIV Antibodies / Q000096:biosynthesis; D015658:HIV Infections / Q000821:virology; D019427:HIV Integrase / Q000235:genetics*; D015497:HIV-1 / Q000235:genetics* / Q000472:pathogenicity* / Q000502:physiology; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000821:virology; D008253:Macaca mulatta; D016296:Mutagenesis; D010957:Plasmids; D012367:RNA, Viral / Q000032:analysis; D017423:Sequence Analysis, RNA; D015302:Simian Immunodeficiency Virus / Q000235:genetics* / Q000472:pathogenicity* / Q000502:physiology; D014162:Transfection; D019562:Viral Load; D014779:Virus Replication
D015483:HIV Antibodies; D012367:RNA, Viral; D019427:HIV Integrase; C514801:p31 integrase protein, Human immunodeficiency virus 1