AEGiS-11IAC: Accelerated loss of telomere length in HIV infection.

11th International AIDS Conference

Vancouver, British Columbia — July 7-12, 1996

Accelerated loss of telomere length in HIV infection.

Int Conf AIDS 1996 Jul 7-12; 11:9 (abstract no. We.A.263)
Wolthers KC, Otto SA, Meyaard L, Miedema F; Dept. of Clinical Viro-Immunology, Central Laboratory of the Netherlands Red Cross Blood Transfusion Service and Laboratory for Exp. & Clin. Immunology of the University of Amsterdam, Amsterdam, The Netherlands, Holland. Fax: 31-20-5123310.

OBJECTIVE: In HIV infection, CD4+ T cell turnover is thought to be as high as 1.8 x 109 per day and it is assumed that during progression, the balance between destruction and renewal of CD4+ T cells is disturbed. Renewal of CD4+ T cells might be a limiting factor, leading to progressive immune deficiency. As a possible measure of T cell turnover in the natural history of HIV infection, we used telomere length.

METHODS: Until now, we have studied 8 HIV-infected persons logitudinally. Four progressed to AIDS within 5 years and 4 remained asymptomatic for at least 7 years. PBMC from three time points were analyzed, including a preseroconversion sample. Sequential PBMC samples taken in a 5 to 8 year period from 4 healthy persons were tested as controls. Cross-sectionally, purified CD4+ and CD8+ T cells from 8 HIV-infected persons and 7 healthy controls were analyzed. HMW DNA digested with BglII was blotted and hybridized with the subtelomeric probe pTH2(de Lange et al, Mol. Cell. Biol. 10:518-527).

RESULTS: In HIV-infected persons, PBMC mean telomeric terminal restriction fragment (TRF) length was found to decrease by 0.6 to 3.8 kb over a period of 5 to 8 years. In contrast, in healthy controls, PBMC TRF length was stable over the same period. Within individuals, no difference in TRF length was found between CD4+ and CD8+ T cells, neither in HIV-positive individuals nor in healthy controls.

CONCLUSION: We obtained evidence for an accelerated loss of TRF length in HIV infection. The loss of TRF length in healthy donors is estimated to be in the order of 40-50 bp/year. Thus, a loss of 1-3 kb, as seen in HIV infection over 5-8 years, is comparable with a loss of TRF over 20-75 years in normal individuals. Our data are in agreement with a rapid turnover of T cells in HIV infection.

Keywords: AEGIS, HIV Infections, Telomere, Acquired Immunodeficiency Syndrome, T-Lymphocytes, HIV Seropositivity, ICA11

960707
WeA263