Telomere dynamics in monkeys: Increased cell turnover in macaques infectedwith chimeric simian-human immunodeficiency viruses

To address the question of how cell turnover is affected by retroviral infe ctions, we used the telomeric terminal restriction fragments (TRFs) as mark ers of cell replicative history and measured their length in macaques infec ted with chimeric simian-human immunodeficiency viruses (SHIVs). The TRF le ngths of mononuclear cells in 104 samples, including longitudinal samples f rom nine cynomolgus and ten pig-tailed macaques infected with SHIV, and in samples from 26 uninfected macaques, were quantitated by an improved method , based on two-dimensional calibration of DNA sizes, pulsed field electroph oresis, and high-resolution Southern blot images. The average TRF lengths o f peripheral blood mononuclear cells (PBMCs) from uninfected pig-tailed (14 .9 +/- 1.6 kbp) and cynomolgus (14.1 +/- 1.8 kbp) macaques were about 3 and 5 kbp longer than those of human infants and 30-year-old adults, respectiv ely. The rate of TRF length shortening in infected pigtailed macaques was s ignificantly (P = 0.035) higher (2.2-fold) than in uninfected monkeys. The TRFs in SHIV-infected cynomolgus monkeys, which, in general, had lower vira l loads than pig-tailed macaques, shortened on average more rapidly (1.6-fo ld) than in uninfected animals, but the difference was not statistically si gnificant. The TRFs of mononuclear cells from the lymph nodes of two rapidl y progressing SHIV-infected macaques that developed AIDS and died also shor tened in parallel but somewhat more rapidly than in the PBMCs. These result s suggest that the rate of PBMC turnover in macaques could be increased sev eral-fold during infections by immunodeficiency viruses, likely due to immu ne activation by SHIV antigens.