Abstract:
:The V3 region of the HIV-1 envelope (Env) glycoprotein gp120 is a key functional domain yet it exhibits distinct mutational patterns across subtypes. Here an invariant residue (Ile 309) was replaced with Leu in 7 subtype C patient-derived Envs from recent infection and 4 related neutralizing antibody escape variants that emerged later. For these 11 Envs, I309L did not alter replication in primary CD4 T cells; however, replication in monocyte-derived macrophages was enhanced. Infection of cell lines with low CD4 or CCR5 revealed that I309L enhanced utilization of CD4 but did not affect the ability to use CCR5. This CD4-enhanced phenotype tracked with sensitivity to sCD4, indicating increased exposure of the CD4 binding site. The results suggest that Ile 309 preserves a V3-mediated masking function that occludes the CD4 binding site. The findings point to an immune evasion strategy in subtype C Env to protect this vulnerable immune target.
journal_name
Virologyjournal_title
Virologyauthors
Lynch RM,Rong R,Li B,Shen T,Honnen W,Mulenga J,Allen S,Pinter A,Gnanakaran S,Derdeyn CAdoi
10.1016/j.virol.2010.04.010subject
Has Abstractpub_date
2010-08-15 00:00:00pages
59-70issue
1eissn
0042-6822issn
1096-0341pii
S0042-6822(10)00245-Xjournal_volume
404pub_type
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