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Next step in creating HIV-1 immunotherapy using fossil virus


Next step in creating HIV-1 immunotherapy using fossil virus
July 17, 2014

The road to finding a cure for HIV-1 is not without obstacles. However, thanks to cutting-edge research by Douglas Nixon, M.D., Ph.D., and colleagues, performed at the George Washington University (GW), Oregon Health & Science University, the University of Rochester, and UC San Francisco, the scientific community is one step closer to finding a viable immunotherapy option for HIV-1, using an immune attack against a fossil virus buried in the genome.

A major hurdle in eradicating HIV-1 has been outsmarting the frequent mutations, or changing coats of the virus caused by its high rate of replication. Researchers have focused on neutralizing antibodies directed against the HIV-1 envelope in order to stop the virus, but the antibodies haven't been able to keep up with this constant change. Nixon's research team found that the right antibody directed against an ancestral fossil virus buried within everyone's genomes might be able to target HIV-1 and neutralize it.
"What we've found is an antibody that recognizes these fossil viruses within all our genomes, which can neutralize HIV-1 in a way that has never been seen before," said Nixon, chair of the Department of Microbiology, Immunology, and Tropical Medicine at the GW School of Medicine and Health Sciences. "We have found in vitro, in the test tube, that you can actually have an antibody work against HIV-1, which is not directed against the HIV-1 virus itself."
In his research, Nixon and colleagues found that by targeting the fossil virus -- an ancestral version of a retrovirus that has become a largely useless part of our DNA -- that these antibodies could focus on a single fixed envelope, as it does not change like the constant changes of HIV-1's envelope outer coat. This discovery provides a new, therapeutic target to beat this particular coat, or variation.

I understand nothing. How can we target a fixed envelope with an antibody and be able to neutralize HIV and its constantly changing envelope ?

Yep, that press release is awfully written. Didn't understand a word either when I first read it.

Here's the abstract of the actual article: An Antibody Recognizing Ancestral Endogenous Virus Glycoproteins Mediates Antibody-Dependent Cellular Cytotoxicity on HIV-1–Infected Cells

In the human genome there are evolutionary leftovers of some retroviruses ('fossil virus'). Some non-functional, distant relatives of HIV. They do not produce complete viral particles anymore, but individual genes may still be transcribed and translated into the corresponding proteins.
Researchers found out that in HIV-infected cells, HIV apparently 'accidentally' triggers the expression of those old retroviral genes. The resulting proteins are presented on the surface of the host cell (usually the CD4-cell) and thus visible to the immune system. These proteins are membrane proteins that are related to the glucoprotein complex of HIV (gp41+gp120).
In the publication mentioned above, researchers now found an antibody that can bind to those ancient proteins and thus trigger the destruction of the infected cell by the immune system. The advantage, they say, is that while HIV constantly mutates and thus antibodies directly aimed at HIV-envelope proteins may become useless, the antibody they found against the ancient membrane protein will not be vulnerable to mutation because unlike HIV, those old genes do not mutate.

I simplified a bit, but that's what I got...

Thank you. It is clearer now.

Very interesting finding but I doubt that latent proviral DNA could be reduced in this way. Indeed latent HIV don't produce virions or proteins...


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