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New provided evidence to settle the arguments between Nef and DCs of HIV-1
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2012-08-22

Human immunodeficiency virus infection / Acquired immunodeficiency syndrome (HIV/AIDS) is a disease of the human immune system caused by the human immunodeficiency virus. HIV has its high genetic variability and can be divided into two major types, HIV-1 and HIV-2. HIV-1 is the most common and pathogenetic strain of the virus.

For the pathology of HIV-1, dentritic cells (DCs), which were first found by Ralph Steinman and Zanvil Cohn in 1973, is featured by its powerful influence in initiating and modulating immune responses. Located at the boundary between the inside and outside environments, DCs provide one bridge between innate and adaptive immunity. As a result, DC is both the first immune cell and the earliest infected target cell. Meanwhile, as an accessory protein of HIV-1, Nef has also been illustrated as a major determinant of the pathology HIV-1, which is a critical immunosuppressive factor for HIV-1 replication, survival and development of AIDS following HIV-1 infection.

Although the first case of human AIDS was found early in 1981, the underling mechanisms are still not clear. One basic but still controversial question is if Nef could influence the function of dentritic cells (DCs) or not.

To help answering this question, Dr. GUO Yan and his colleagues (Kunming Institute of Zoology, the CAS) used THP-1 (human monocytic leukemia cell line) as monocytic DC precursors toinvestigate how overexpression of HIV-1 Nef influences the processes of differentiation and maturation of DCs. The result demonstratedthat long-lasting expression of Nef at high levels indeed retards differentiation and maturation of dendritic cells in terms of phenotype and morphology. It is also provided the basis for further study into DCs’ immunological functions in HIV-1 infectious situations. According to Dr. Guo, it is hopeful that potentially, stable expression of intracellular Nef in vivo may function as a subtle mode to support long-lasting HIV-1 existence.

Moreover, this study, for the first time, has reported that intracellular expression of HIV-1 Nef impairs differentiation and maturation from THP-1 to DCs. And it is also very helpful to settle the arguments raised by numerous studies on how HIV-1 interferes with immunological functions of DCs.

The main findings of this study have been published on PLos ONE [7(7): e40179, 2012](http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0040179).

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