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Natural block for HIV infection

Currently, there are over 36 million HIV-infected individuals worldwide and hundreds of thousands die of HIV-related diseases annually. Understanding the mechanism behind HIV-1 tropism may provide cues for anti-viral treatments.
Natural block for HIV infection
Despite years of research, we are no closer to developing an effective anti-HIV vaccine, while treatments so far have failed to eradicate the virus. HIV-1 has a narrow host tropism limited to humans and chimpanzees due to several barriers to viral replication in other species. These barriers comprise host factors required for virus replication and dominant-acting factors that block replication in many species. The latter are also known as restriction factors (RF) and are part of the intrinsic antiviral immunity.

With this in mind, scientists on the EU-funded HIVMARMOD (Innate intracellular blocks to HIV-1 in New World monkeys) set out to investigate which factors block HIV-1 replication in marmoset New World monkey cells. Previous work had indicated that HIV-1 infection was blocked at the level of viral entry.

HIVMARMOD further showed that a number of marmoset proteins (A3G, BST2) prohibited HIV-1 infection in cell culture. However, after a process of adaptation in cell culture, specific changes in the viral proteins Vif and Env facilitated the escape of the virus from A3G and BST2, respectively. Insight into the mechanism behind this observation indicated that Env variants increased viral fitness and favoured cell-to-cell transmission.

Additionally, scientists observed that marmoset peripheral blood lymphocytes (PBLs) and a B lymphocytic cell line (B-LCL) contained extra post-entry viral blocks. In PBLs, the block occurred at the level of reverse transcription, reducing the accumulation of early and late viral transcripts. In the case of B-LCL, an RF inhibited provirus integration into the host genome.

Taken together, the HIVMARMOD activities provided new insights into viral-host interactions and the mechanisms that the virus uses to evade innate immune response. Characterisation of the mechanism of action of these RFs could help comprehend HIV pathology and assist in the discovery of novel therapies against infection.

Related information

Subjects

Life Sciences

Keywords

HIV infection, tropism, restriction factor, marmoset, new world monkeys, A3G, BST2, Vif, Env
Record Number: 188719 / Last updated on: 2016-10-26
Domain: Biology, Medicine
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