Method: The HIV Gag p24 TL9 peptide (TPQDLNTML180-188), the escape variant Q182S, Q182T, T186S, and Q182S/T186S TL9 peptide were synthesized at > 95% purity, were synthesized at GL Biochem corporation and confirmed by high-performance liquid chromatography.
Paediatric non-progression following grandmother-to-child HIV transmission.
Result: Structural analysis indicates likely mechanism of L188F and T186S impact on VRC.
Result: To investigate the possibility that this rare L188F mutant might similarly affect VRC, thereby contributing to slow progression observed in subjects GD and D2, this variant was generated by site-directed mutagenesis and the replicative capacity compared with the more common and well-described HLA-B*81:01-associated TL9 escape mutants, T186S, the combination of T186S/ Discussion: The studies described here are highly consistent with these findings, in demonstrating, first, the dramatic negative impact of L188F, as well as T186S, on viral replicative capacity; and, second, the striking influence of viral sequence context.
A molecular switch in immunodominant HIV-1-specific CD8 T-cell epitopes shapes differential HLA-restricted escape.
Introduction: The mutation principally responsible for this protective effect is the above-mentioned HLA-B*81:01-driven T186S variant that fails to yield replicating virus stocks in studies of C clade virus.
Result: Of note, selection for the above-mentioned T186S at position 7 of th
Figure: (E, F) Intraepitope HIV-1 polymorphisms for (E) TL9-p24 shown on the X-axis for Q182X as peptide position 3 and T186S as position 7 and (F) for RM9-Nef R71K as for peptide position 1 and L76X as position 6 and expressed as the percentage of total viral sequences for n = 1,327 HIV-1 infected individuals of which n = 189 expressed HLA-B*07:02, n = 436 expressed HLA-B*42:01, n = 56 expressed HLA-B*42:02 and n = 213 expressed HLA-B*81:01.
Impact of HLA-B*81-associated mutations in HIV-1 Gag on viral replication capacity.
Abstract: Constructs encoding the T186S mutation in combination with other putative compensatory mutations were attenuated or defective.
Abstract: Engineering of the T186S mutation alone into all patient-derived subtype C sequences failed to yield replication-competent viruses, while in the subtype B sequence, the T186S mutation resulted in impaired replication capacity.
Abstract: In addition, we investigated potential compensatory effects of various polymorphisms, including other HLA-B*81-associated mutations that significantly covary with the T186S mutation.
Abstract: Only the T186S mutation in combination with the T190I mutation yielded replication-competent viruses for all virus backbones tested; however, these constructs replicated slower than the wild type, su
Progression to AIDS in South Africa is associated with both reverting and compensatory viral mutations.
1Abstract: This is associated with preserved selection pressure at specific viral amino acids (e.g., the T242N polymorphism within the HLA-B*57/5801 restricted TW10 epitope), but with reversion at other sites (e.g., the T186S polymorphism within the HLA-B*8101 restricted TL9 epitope), most notably in Gag and suggestive of ""immune relaxation""."
Abstract: Mutations at HIV Gag T186S and T242N reduced VRC, however, in advanced disease only the T242N mutants demonstrated increasing VRC, and were associated with compensatory mutations (p = 0.013).
HIV mutation literature information.
PMID: 
2022
Frontiers in immunology
Browser Board
Co-occurred Entities
Filtrator
ViMRT