Characterization of proviral DNA from an individual with long-term, nonprogressive infection with HIV-1 and nonrecoverable virus.

Abstract

A small proportion of individuals infected with HIV-1 known as long-term nonprogressors (LTNPs) remain healthy and immunologically normal, with stable numbers of CD4+ lymphocytes, for prolonged periods without the administration of antiretroviral agents. The long terminal repeat (LTR) of HTV-1 proviral DNA of an LTNP from whom virus was consistently not recoverable has now been isolated by a nested polymerase chain reaction (PCR) method and shown to contain a total of 38 point mutations, only four of which affect promoter and enhancer elements, compared with the IIIB strain of HIV-1. Almost the entire HIV-1 proviral DNA was then isolated from the proband by a long PCR approach. Restriction enzyme digestion of the proviral DNA revealed no large deletions in the gag, pol, or env genes, although the loss of an Nco I site was apparent. Amplification of the env gene by long PCR also yielded a product apparently identical in size to that obtained with HIV-1 strain IIIB. Analysis by long PCR of HIV-1 proviral DNA from LTNPs with nonrecoverable virus may clarify the mechanism of long-term nonprogression and contribute to the development of HIV-1 vaccines.