Analysis of a Primary Isolate-like Virus from Simian and Human Immunodeficiency Virus-Infected Macaque Having Broad Neutralizing Activity

To investigate the changes of neutralizing antibodies and viruses during simian and human immunodeficiency virus (SHIV) infection, we examined the cross-neutralizing ability of sequential sera from three macaques infected with SHIV, NM-3rN, and analyzed the sensitivity of the reisolate to neutralizing antibodies. Neutralizing activities of macaques' sera against the parental HIV-1 showed a persistent increase. Neutralizing activities were highly strain specific, but the spectrum of the neutralizing activity expanded against various clades of primary HIV-1s at 3 years after infection in one of the three macaques. The reisolate from an NM3-rN-infected macaque at 56 wpi, designated as R4356, was neutralized by sera from this macaque at a much lower titer than NM-3rN, even by the sera collected 2 years after the reisolation. Sera from macaques that were newly infected with R4356 also did not neutralize R4356 despite neutralizing NM-3rN strongly. These results suggested that long-term persistent infection with SHIV induced neutralizing antibodies with a broad spectrum. However, a virus resistant to the neutralizing antibodies emerged in the persistently infected macaque.