Adaptation of HIV-1 to cells expressing rhesus monkey TRIM5α.
The cross-species transmission of retroviruses is limited by host restriction factors that exhibit inter-species diversity. For example, the TRIM5α proteins of Old World monkeys block the early, post-entry steps in human immunodeficiency virus (HIV-1) infection. We adapted an HIV-1 isolate to replicate in cells expressing TRIM5α(rh) from rhesus monkeys, an Old World species. A single amino acid change in the cyclophilin-binding loop of the HIV-1 capsid protein allowed virus replication in cells expressing TRIM5α(rh). The capsid of the escape virus exhibited a reduced affinity for TRIM5α(rh), but retained the ability to bind cyclophilin A efficiently. Thus, a preferred HIV-1 escape pathway involves decreased binding to TRIM5α, a capsid-destabilizing factor, and retention of binding to cyclophilin A, a capsid-stabilizing factor.
Pacheco
Beatriz
B
Department of Cancer Immunology and AIDS, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA 02115, USA.
Finzi
Andrés
A
Stremlau
Matthew
M
Sodroski
Joseph
J
D000222:Adaptation, Physiological / Q000235:genetics; D000818:Animals; D036022:Capsid Proteins / Q000378:metabolism; D021984:Cyclophilin A / Q000378:metabolism; D015497:HIV-1 / Q000235:genetics / Q000472:pathogenicity* / Q000502:physiology*; D006367:HeLa Cells; D006801:Humans; D008253:Macaca mulatta; D008958:Models, Molecular; D046912:Multiprotein Complexes; D009154:Mutation; D011506:Proteins / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D013045:Species Specificity; D044767:Ubiquitin-Protein Ligases; D014779:Virus Replication / Q000235:genetics / Q000502:physiology
D036022:Capsid Proteins; D046912:Multiprotein Complexes; D011506:Proteins; D011994:Recombinant Proteins; C482587:TRIM5(alpha) protein, rhesus monkey; D044767:Ubiquitin-Protein Ligases; D021984:Cyclophilin A