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New clues to explain mechanism of HIV infection in pig-tailed macaques

Recent studies made by a group of CAS scientists may shed light on a new approach for demystifying the complicated pathogenesis of the AIDS, i.e., the formative mechanism of HIV infection at the molecular level. The pioneering work provides new clues for stemming the genetic pathway needed for propagation of the killer epidemic. The research result has been published by two monographic journals AIDS and Gene respectively.

  The new findings are jointly achieved by two research teams headed by Dr. ZHENG Yongtang and Dr. SU Bing, with the Key Laboratory of Cellular & Molecular Evolution and Key Laboratory of Animal Models and Human Disease Mechanisms, both being attached to the CAS Kunming Institute of Zoology (KIZ). Their exploration is targeted on the pig-tailed macaque (Macaca nemestrina), the only known non-human species of Old World primates genetically vulnerable to the HIV-1 infection.

  In order to make clear the pathogenic details of AIDS, it is critical for scientists to find an ideal animal model for conducting necessary tests and based on this, both anti-HIV drugs and vaccines can be developed. Until now, however, one of major stumbling blocks for advancing the HIV/AIDS research lies in the lack of such an ideal animal model. On the other hand, more and more lab evidences have shown that, the anti-reverse transcription viral protein in the host's body is a natural screen to stem the HIV infection and the restrictive factors behind this phenomenon are found them to react on different phases identified by scientists in a period of the genomic replication occurring in the HIV-I virus. In recent years, scientists discovered TRIM5α, a kind of molecules of natural immunity in the Old World monkeys that exhibits a strong resistance to suppress such a replication after the HIV-I virus makes its way into the host cells. This fact may explain why almost all species of the Old World primates are able to get rid of the HIV infection while the pig-tailed macaque is the only exception as it is found susceptible to the infection in AIDS epidemiology.

  In the teamwork formed by the two research teams at KIZ, the scientists carried out an analytic study on the genomic sequencing and expression of the TRIM5α gene sampled from the pig-tailed macaque, leading to the identification of a novel isoform gene of the fusion between TRIM5α and Cyclophilin A, whose cDNA was inserted into the former's locus. Then the TRM5-CypA fusion gene (mnTRIMCyp) was cloned into the pcDNA3.1(+) expression vector. The protein products derived from mnTRIMCyp were found unable to block the propagation of the HIV-I infection and its replication. Based on this, the scientists speculate this should be the molecular mechanism, in which the pig-tailed macaque's vulnerability to the HIV-I infection very probably is rooted.

  The research conclusion elucidates some functional details of the mechanism why TRIM5α can inhibit the HIV-I infection and its replication and therefore provides an approach for the development of a more ideal non-human primate model to support the human struggle against the curse of HIV/AIDS infection as a focus of public health concern in today's world.

  The research itself is an R&D project jointly funded by the National Foundation for Natural Sciences of China and the National Key Basic Research Program (dubbed the National "973" Program).


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