Cytopathicity of human immunodeficiency virus type 1 primary isolates depends on coreceptor usage and not patient disease status

It has been hypothesized that human immunodeficiency virus type 1 (HIV-1) e volves toward increased cytopathicity in conjunction with disease progressi on in infected patients. A viral property known to evolve in some but not a ll patients is coreceptor utilization, and it has been shown that a switch in coreceptor utilization is sufficient for the development of increased cy topathicity. To test the hypothesis that the evolution of other viral prope rties also contributes to accelerating cytopathicity in vivo, we used human lymphoid tissue explants to assay the cytopathicity of a panel of primary HIV-1 isolates derived from various stages of disease characterized by the presence or absence of changes in coreceptor preference. We found no eviden ce of coreceptor-independent increases in cytopathicity in isolates obtaine d either before coreceptor preference changes or from patients who progress ed to AIDS despite an absence of coreceptor evolution. Instead, the cytopat hicity of all HIV-1 isolates was determined solely by their coreceptor util ization. These results argue that HIV-1 does not evolve toward increased cy topathicity independently of changes in coreceptor utilization.