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Virus Evolution and Neutralization Sensitivity in an HIV-1 Subtype B' Infected Plasma Donor with Broadly Neutralizing Activity.

ABSTRACT: We sought to analyze the evolutionary characteristics and neutralization sensitivity of viruses in a human immunodeficiency virus type 1 (HIV-1) subtype B' infected plasma donor with broadly neutralizing activity, which may provide information for new broadly neutralizing antibodies (bNAbs) isolation and immunogen design. A total of 83 full-length envelope genes were obtained by single-genome amplification (SGA) from the patient's plasma at three consecutive time points (2005, 2006, and 2008) spanning four years. In addition, 28 Env-pseudotyped viruses were constructed and their neutralization sensitivity to autologous plasma and several representative bNAbs were measured. Phylogenetic analysis showed that these env sequences formed two evolutionary clusters (Cluster I and II). Cluster I viruses vanished in 2006 and then appeared as recombinants two years later. In Cluster II viruses, the V1 length and N-glycosylation sites increased over the four years of the study period. Most viruses were sensitive to concurrent and subsequent autologous plasma, and to bNAbs, including 10E8, PGT121, VRC01, and 12A21, but all viruses were resistant to PGT135. Overall, 90% of Cluster I viruses were resistant to 2G12, while 94% of Cluster II viruses were sensitive to 2G12. We confirmed that HIV-1 continued to evolve even in the presence of bNAbs, and two virus clusters in this donor adopted different escape mechanisms under the same humoral immune pressure.

SUBMITTER: Hu Y

PROVIDER: S-EPMC8064334 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BACKGROUND: HIV-1 subtype B' isolates have been predominantly circulating in China. Their intra- and inter-subtype neutralization sensitivity to autologous and heterologous plasmas has not been well studied. RESULTS: Twelve HIV-1 B' clinical isolates obtained from patients were tested for their intra- and inter-subtype neutralization sensitivity to the neutralization antibodies in the plasmas from patients infected by HIV-1 B' and CRF07_BC subtypes, respectively. We found that the plasmas from the HIV-1 B'-infected patients could potently neutralize heterologous viruses of subtype B' with mean ID50 titer (1/x) of about 67, but they were not effective in neutralizing autologous viruses of subtype B' with mean ID50 titer (1/x) of about 8. The plasmas from HIV-1 CRF07_BC-infected patients exhibited weak inter-subtype neutralization activity against subtype B' viruses with ID50 titer (1/x) is about 22. The neutralization sensitivity of HIV-1 B' isolates was inversely correlated with the neutralizing activity of plasmas from HIV-1 B'-infected patients (Spearman's r = -0.657, P = 0.020), and with the number of potential N-glycosylation site (PNGS) in V1-V5 region (Spearman's r = -0.493, P = 0.034), but positively correlated with the viral load (Spearman's r = 0.629, P = 0.028). It had no correlation with the length of V1-V5 regions or the CD4+ T cell count. Virus AH259V has low intra-subtype neutralization sensitivity, it can be neutralized by 17b (IC50: 10?g/ml) and 447-52D (IC50: 1.6?g/ml), and the neutralizing antibodies (nAbs) in plasma AH259P are effective in neutralizing infection by the primary HIV-1 isolates with different subtypes with ID50 titers (1/x) in the range of 32-396. CONCLUSIONS: These findings suggest that the HIV-1 subtype B' viruses may mutate under the immune pressure, thus becoming resistant to the autologous nAbs, possibly by changing the number of PNGS in the V1-V5 region of the viral gp120. Some of primary HIV-1 isolates are able to induce both intra- and inter-subtype cross-neutralizing antibody responses.

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Virus Evolution and Neutralization Sensitivity in an HIV-1 Subtype B' Infected Plasma Donor with Broadly Neutralizing Activity.

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