RESUMO
Dozens of broadly neutralizing antibodies (bnAbs) have been identified from chronically infected HIV-1 patients, but it is still unclear what determines the acquisition of broad neutralizing activities. Two chronic HIV-1 infected cases with similar autologous neutralizing activities were followed up for two years to study the viral evolution of the envelope gene and the neutralizing activity against autologous and heterologous viruses. The neutralization activities against homologous viruses gradually increased in both patients. HA172 eventually developed a cross-clade neutralizing antibodies response, with a neutralization breadth of 88.9% (8/9) against tier 2 heterologous HIV-1. However, HA084 could only neutralize 44.4% (4/9) of the same virus panel. Higher genetic diversity of the env gene at baseline (0.027 vs. 0.002, p ï¼ 0.001), stronger immune pressure on V3 (3.08 vs. 0.99, p ï¼ 0.001) or V4 loops (2.63 vs. 0.62, p = 0.002), increasing length of V1V2 and V4 loops, and evolution on V1V2 and CD4-binding sites (CD4bs) were identified in HA172. The findings demonstrated that higher viral genetic diversity, viral evolution on V1V2 and CD4bs might contribute to the development of bnAbs. The findings indicate the possibility of inducing better neutralizing antibodies in immunodeficient patients and may help develop an immune therapy strategy based on bnAbs.
Assuntos
Anticorpos Neutralizantes/sangue , Variação Genética , Anticorpos Anti-HIV/sangue , Infecções por HIV/imunologia , Infecções por HIV/virologia , Produtos do Gene env do Vírus da Imunodeficiência Humana/genética , Produtos do Gene env do Vírus da Imunodeficiência Humana/imunologia , Formação de Anticorpos , HIV-1/genética , HIV-1/imunologia , Humanos , MasculinoRESUMO
OBJECTIVE: To evaluate the coreceptor usage characters and evolution of human immunodeficiency virus-1 (HIV-1) primary infection. METHODS: A total of 12 HIV-1 primary infection cases were recruited from a high-risk population for this prospective cohort trial. The blood samples were collected at the earliest time after infection and after a viral setpoint respectively. RNA was extracted from plasma. The env genes were amplified through reverse transcription-PCR (RT-PCR) and nested PCR. And the env fragments were ligated to T vector and then sequenced. The pattern of coreceptor usage was predicted with five different online tools. RESULTS: Among them, 11 were predicted as CCR5 virus transmission and 1 as CXCR4 virus transmission. The viruses in 1 case were detected as a switch of coreceptor usage from CCR5 to CXCR4. The consistency of five different prediction rules was 88.3%. CONCLUSION: Although the CCR5 usage virus is predominant in primary infection through sexual transmission, CXCR4 usage virus can also be detected. A switch of coreceptor usage may happen within the first year post-infection. Adopting multiple rules may improve the efficiency and validity for the prediction of coreceptor usage based on genotypes.
