- Autores: Antunes F, Barroso H, Borrego P, Doroana M, Marcelino JM, Nilsson C, Novo C, Taveira N
- Journal: AIDS Research and Human Retroviruses
- Link: https://apps.webofknowledge.com/full_record.do?product=UA&search_mode=GeneralSearch&qid=1&SID=W1nslz6EeRqf8Bzyzm3&page=1&doc=1
Title Escape from neutralization is a frequent event in HIV-2 infection and is strongly associated with X4 tropism. Background HIV-2 infection induces the production of a broad neutralizing antibody (NAb) response and this has been linked to a better control of viral replication and disease progression. However, little is known about the neutralizing targets and the dynamics of the NAb response and viral escape from neutralization during HIV-2 infection. This study was set out to investigate these issues. Methods A cohort of 28 HIV-2 infected patients followed during 4 years was analyzed. Autologous and heterologous neutralizing activities were determined with purified IgG antibodies in a TZM-bl cells-based assay against patient uncloned viruses. Coreceptor usage of the viruses was determined in GHOST cells. The sequence of the C2, V3 and C3 env regions was determined for all patients. Results Twenty-four new primary isolates were obtained from 12 patients. Most patients (8 out of 12) were infected with R5-viruses; the remaining 4 patients harbored X4-viruses. Autologous NAbs (median IC50 = 3.91 microgram/ml; range = 0.049-38 microgram/ml) were detected only in 6 patients, all infected with R5-viruses. Most (4/6) patients unable to produce autologous NAbs were infected with X4-viruses. All but one patient produced NAbs targeting heterologous R5-viruses. The heterologous Nab response differed widely in potency between patients (median IC50 = 4.14 microgram/ml; range = 0.049-49.08 microgram/ml). Remarkably, however, none of the patients produced antibodies against X4-viruses. A limited set of amino acids located in the V3 loop was associated with X4 tropism and resistance to neutralization. Conclusions Heterologous neutralization in HIV-2 patients is restricted to R5 isolates. Escape from autologous neutralization is a frequent event in HIV-2 infection and is strongly associated with X4 tropism. Viral determinants of neutralization resistance and X4 tropism seem to be located in the V3 region. These results have clear implications for the design of HIV-2 vaccine immunogens able to elicit the production of broadly reactive neutralizing antibodies.