Recent telomere length studies at UCLA have shown that CD4+ and CD8+ T lymphocytes extracted from HIV-1 infected individuals exhibited diverging patterns of telomere shortening. CD4+ T cells did not exhibit telomere shortening and retained high telomerase activity whereas CD8+ T cells showed telomere lengths as short as those found in T cells that reach replicative senescence. These results are difficult to reconcile with reports of high T cell turnover in HIV-1 infected individuals but suggest that the virus may have evolved a mechanism to influence telomerase dynamics.

Given that specific proteins of HIV-1 have transcriptional influence, UCLA scientists began to study their effects on telomerase dynamics. What they found was that the addition of a highly purified HIV-1 protein to uninfected lymphocytes resulted in the same diverging patterns of telomere shortening as they had observed in the lymphocytes from HIV-1 infected patients. The results indicate that a specific HIV-1 protein and not another component, independently modulates telomerase activity. To determine whether this protein had any effect on transformed cells, various tumor cells were exposed to the purified protein. Again, they obtained the same diverging patterns, for which the up-regulation of telomerase may account for the increased incidence of neoplasia associated with HIV-1 disease and the down-regulated effects may be of therapeutic significance. Moreover, the acceleration of tumor development from exposure to the protein suggests that HIV-1 may potentially be an oncogenic virus.

Elucidation of the mechanistic basis of the relationship between this protein and telomerase may yield information on the poorly understood genetic control of telomerase induction, an area that is of significant relevance to cancer, immunotherapy, and stem cell expansion.

Reference: UCLA Case No. 1999-556