Reversal of human immunodeficiency virus type 1 IIIB to a neutralization-resistant phenotype in an accidentally infected laboratory worker with a progressive clinical course

The role of humoral immunity in controlling human immunodeficiency virus ty pe 1 (HIV-1) is still controversial. The resistance of primary HIV-1 varian ts to neutralization by antibodies, sera from HIV-1-infected patients, and soluble CD4 protein has been suggested to be a prerequisite for the virus t o establish persistence in vivo. To further test this hypothesis, we studie d the neutralization sensitivity of two IIIB/LAV variants that were isolate d from a laboratory worker who accidentally was infected with the T-cell-li ne-adapted neutralization-sensitive IIIB isolate. Compared to the original virus in the inoculum, the reisolated viruses showed an increased resistanc e to neutralization over time. The ratio of nonsynonymous to synonymous nuc leotide substitutions in the envelope gene pointed to strong positive selec tion. The emergence of neutralization-resistant HIV preceded disease develo pment in this laboratory worker. Our results imply that the neutralization resistance of primary HIV may indeed be considered an escape mechanism from humoral immune control.