Binding and susceptibility to postentry restriction factors in monkey cells are specified by distinct regions of the human immunodeficiency virus type 1 capsid.
In cells of Old World and some New World monkeys, dominant factors restrict human immunodeficiency virus type 1 (HIV-1) infections after virus entry. The simian immunodeficiency virus SIV(mac) is less susceptible to these restrictions, a property that is determined largely by the viral capsid protein. For this study, we altered exposed amino acid residues on the surface of the HIV-1 capsid, changing them to the corresponding residues found on the SIV(mac) capsid. We identified two distinct pathways of escape from early, postentry restriction in monkey cells. One set of mutants that were altered near the base of the cyclophilin A-binding loop of the N-terminal capsid domain or in the interdomain linker exhibited a decreased ability to bind the restricting factor(s). Consistent with the location of this putative factor-binding site, cyclophilin A and the restricting factor(s) cooperated to achieve the postentry block. A second set of mutants that were altered in the ridge formed by helices 3 and 6 of the N-terminal capsid domain efficiently bound the restricting factor(s) but were resistant to the consequences of factor binding. These results imply that binding of the simian restricting factor(s) is not sufficient to mediate the postentry block to HIV-1 and that SIV(mac) capsids escape the block by decreases in both factor binding and susceptibility to the effects of the factor(s).
Owens
Christopher M
CM
Department of Cancer Immunology and AIDS, Dana-Farber Cancer Institute, 44 Binney Street, Boston, MA 02115, USA.
Song
Byeongwoon
B
Perron
Michel J
MJ
Yang
Peter C
PC
Stremlau
Matthew
M
Sodroski
Joseph
J
D000595:Amino Acid Sequence; D000818:Animals; D002213:Capsid / Q000737:chemistry* / Q000378:metabolism; D021984:Cyclophilin A / Q000378:metabolism*; D016572:Cyclosporine / Q000494:pharmacology; D004198:Disease Susceptibility; D015683:Gene Products, gag / Q000378:metabolism; D015497:HIV-1 / Q000737:chemistry / Q000472:pathogenicity*; D006801:Humans; D008253:Macaca mulatta; D008969:Molecular Sequence Data; D015302:Simian Immunodeficiency Virus / Q000737:chemistry / Q000472:pathogenicity; D013329:Structure-Activity Relationship
D015683:Gene Products, gag; D016572:Cyclosporine; D021984:Cyclophilin A