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HIV-1–induced AIDS in monkeys

Science  20 Jun 2014:
Vol. 344, Issue 6190, pp. 1401-1405
DOI: 10.1126/science.1250761

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Adapting HIV-1 to infect monkeys, too

HIV-1 replicates well in humans but not in monkeys or mice. On the up side, this reduces the risk of cross-species transmissions, but it makes the study of HIV-1 and AIDS more difficult. Hatziioannou et al. overcame this hurdle by serially passaging HIV-1 in pigtailed macaques. Over time, the HIV-1 acquired mutations that allowed it to adapt to the monkeys. Depleting CD8+ T cells during acute infection resulted in a subset of animals developing an AIDS-like disease by the fourth passage. HIV-1 envelope protein gene selection and the acquisition of mutations in the HIV protein Vpu, which allowed HIV-1 to overcome host restriction by the macaque protein tetherin, accompanied the viral adaptation to the monkeys.

Science, this issue p. 1401

Abstract

Primate lentiviruses exhibit narrow host tropism, reducing the occurrence of zoonoses but also impairing the development of optimal animal models of AIDS. To delineate the factors limiting cross-species HIV-1 transmission, we passaged a modified HIV-1 in pigtailed macaques that were transiently depleted of CD8+ cells during acute infection. During adaptation over four passages in macaques, HIV-1 acquired the ability to antagonize the macaque restriction factor tetherin, replicated at progressively higher levels, and ultimately caused marked CD4+ T cell depletion and AIDS-defining conditions. Transient treatment with an antibody to CD8 during acute HIV-1 infection caused rapid progression to AIDS, whereas untreated animals exhibited an elite controller phenotype. Thus, an adapted HIV-1 can cause AIDS in macaques, and stark differences in outcome can be determined by immunological perturbations during early infection.

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