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One More Step Closer to the Possible HIV/AIDS Vaccines

Dec 29, 2011

SIV/HIV (simian/human immunodeficiency virus) is always a distressing topic. What’s the difference of SIV and HIV? In short, HIV is found in humans and SIV is found in non-human simians. SIV, also know as African Green Monkey Virus, is a retrovirus able to infect at least 33 species of African primates. The research found that SIV has been present in monkeys and apes for at least 32,000 years.

Virus strains from two if these primate species, SIVsmm in sooty mangabeys and SIVepz in chimpanzees, are believed to have crossed the species barrier into humans, resulting in HIV-2 and HIV-1, respectively. The most likely route of transmission of HIV-1 to humans involves contact with the blood of chimps that are often hunted for bushmeat in Africa.

Although the research of HIV have went trough more than 27 years, people still cannot understand how the immune systems defend against HIV infection, and, as an upsetting result, no effective vaccine to cure the AIDS could be developed. As the way of discovering the relevant pathological mechanisms of HIV are so difficult, every single step forward should be marked. Recently, Ph.D candidate, XIA Houjun (Kunming Institute of Zoology, the CAS) and his colleagues have done series research on the dendritic cells (DCs) subsets’ population, immuno-phonotype, function and mechanisms of SIVmac239 infected Chinese rhesus macaques (Ch Rhs), which have added knowledge to what people have known about HIV.

Because the SIVmac pathogenesis of Ch Rhs’ are closer to HIV-1 infections in untreated adult humans, they have been used extensively in recent years for HIV study, vaccine research and development. The heterogeneous populations of DCs are differing in location, migratory pathways, and immunological function, and they are essential for innate and adaptive immunity. In general, DCs patrol around the peripheral tissues of the human body and execute their duty of antigen uptake, process, and presentation to naive T-cells. According to the origin, DCs are divided into two main subsets, namely myeloid DCs (mDCs) and plasmacytoid DCs (pDCs), which play a pivotal role in controlling HIV infection and AIDS progression.

XIA’s previous study found that SIVmac239-infected Ch Rhs significantly increased IFN-a and IL-12 production in the acute phase of the infection, which may be the result of an immune activation of DCs subsets. To reveal the in vivo status of the DCs subsets, in present study, they detected the trend of apoptosis and immunophenotype of CD1c+mDCs and pDCs from Ch Rhs during the acutephase of SIVmac239 infection, and found that pDCs were more influenced by SIV infection than CD1c+mDCs. This discrepancy between pDCs and CD1c+mDCs shows the different roles of DCs subsets in AIDS progression.

According to XIA, the pDCs were more prone to apoptosis after infection, which may be due to their high expressions of CD4 and CCR5. Both the DCs subsets showed decreased CD4 expression and enhanced CCR5 expression; particularly, those of pDCs significantly changed at most of the time points. However, no correlation was found in CD1c+mDCs. During this period, the percentage of active CD1c+ mDCs and pDCs obviously increased, following an increase in CCR7. Either CD80 or CD86 expressed on CD1c+ mDCs and pDCs was positively correlated with the plasma viral loads.

In summarym XIA’s analysis not only confirms his conclusion of previous research, but also demonstrates that both DCs subsets activated through elevating the expression of co-stimulatory molecules, which was beneficial in controlling the replication of SIV. However, a mere broad immune activation initiated by activated DCs may lead to tragic AIDS progression.

Main findings of the study have been published on PLoS ONE [6(12): e29036. doi:10.1371/journal.pone.0029036].

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