PLoS Pathog: Significant progress! Identify a potential new reservoir of latent HIV virus

May 12, 2020 /
BioON/--- scientists have long known that even with antiretroviral therapy, some HIV will remain in infected people forever, hidden in the smaller cell bank of the immune system (i.e., the HIV virus library, which refers to HIV integrated into the host immune cell genome without active proliferation)When patients stop treatment, the virus almost always rebounds quickly from the HIV virus, causing deadly symptoms to reappearthese HIV reservoirs remain a major obstacle to the cure of HIV/AIDSHowever, there is no easy way to target virus library cells for removalScientists are also unable to effectively extract virus library cells from patients for research in order to eventually find a way to control themThe reason is that HIV in these cells is latentAs a result, the surfaces of these cells do not carry viral proteins that are easily discovered by the host's immune systemAs a result, scientists have been looking for other ways to pinpoint virus library cellsIn a new study, DrNadia Roan, a visiting scholar at the Institute of Meteorology andImmunology
, described a class of cells that prioritize support for HIV latent infectionThese cells express the surface protein CD127, which is present in tissues such as lymph nodes and is thought to carry more HIV virus in the blood than in the bloodThe findings were recently published in the journal PLoSPres, with the title "CD127 preferentially supportlateHIVeHIVeHIV-1infection"images from PLoSPres, 2020, doi: 10.1371/journal.ppat.1008450"Our results suggest that CD127-positive cells in tissues may be an important target for the cure for HIV infection," Roan said "
in addition, scientists may use cd127 protein to isolate virus cells from patients and study what makes them silence HIV and occasionally reactivate the virus new virus library? HIV targets T cells that are mainly present in lymphnodes and tonsils However, HIV infection studies focused on T cells circulating in the blood, while T cells in the blood were relatively easy to obtain---- and volunteers were more likely to receive blood withdrawals than tissue biopsies But focusing on T-cells present in the blood is likely to skewe scientists' perceptions of the composition of the virus library "For a long time, we have been speculating that there are different types of virus library cells, and that different tissues hold different types of virus library cells, " Says Roan But this has been difficult to prove because the virus library cells in people living with HIV are very rare The vast majority of in vitro HIV latent models use cells in the cell line or circulating in the blood By contrast, Roan and her team have been using tissue samples to study HIV infection In previous research, her team exposed tonsil cells to HIV in the lab to see which cells were most susceptible to infection Using a variety of experimental methods , her team found that tonsil cells expressing the surface protein CD127 can effectively ingest HIV, but rarely replicate it In contrast, tonsil cells that carry CD57 on the other surface are easily supported by effective HIV infection this is interesting, but that doesn't mean CD127-positive cells are viral library cells "After HIV enters the cells, there is still a way for cells to escape infection," said Feng Hsiao, co-author of the paper and a former researcher at Roan Labs "one way is to prevent HIV from replicating its genome Unlike the genomes of human cells, the genomes of HIV are made up of RNA One of the first tasks of the virus after entering the cell was to convert its RNA genome into a corresponding copy of DNA using a viral enzyme called retroviruse cells can block this step by activating an enzyme called SAMHD1, which consumes the component units needed for HIV to replicate its genome (buildingblock, in this case, nucleotides) There is some evidence that this mechanism may play a role in blood cells However, in the new study, Roan and her team found that gene manipulation out of SAMHD1 did not cause CD127-positive cells to produce HIV, even if doing so could promote CD57-positive cells to produce the virus "This suggests that CD127-positive cells prevent the virus from developing later in the HIV life cycle," said Dr Julie Frouard, a postdoctoral fellow at Roan Labs, co-author of the paper "
's preference for latent infections
the next step in HIV is to integrate copies of its genome into the DNA of host cells Once integrated, viral genes can use molecular machines in cells to produce their own proteins and assemble new virus particles to infect other cells virus library cells integrate HIV's genetic material into their own genomes, even though they somehow silence it This occasional movement of genetic material allows the release of infectious HIV Does CD127-positive tonsill cells allow HIV genome integration? to answer this question, the Roan team extracted the genomes of CD127-positive cells and CD57-positive cells exposed to HIV in the lab Using genetic tools that can specifically detect integrated HIV DNA sequences, they found that both types of cells contain copies of the HIV genome, although CD127-positive cells produce far less HIV than CD57-positive cells CD127-positive cells seem to be more inclined to HIV latent infection However, HIV, which is successfully integrated in CD127-positive cells, is not forever silent Roan and her team found that by treating CD127-positive cells infected with HIV latent infection with reagents known to stimulate T cells, they could induce those cells to reactivate HIV As a result, CD127-positive tissue cells are likely to act as a virus library in the body, keeping the virus in a latent state for most of the time, but occasionally activating the virus, releasing seeds for a new infection "The ability of a particular type of tissue T-cell to prioritize support for HIV latent infection is a concern, which can help us learn more about how the virus library in the tissue was initially built," Roan said "
control the virus library
cd127-positive cells are a major component of the virus library in HIV-infected people, pending follow-up research and analysis of these cells from multiple tissue sites The Roan team's initial study is encouraging because they show that CD127 markers on the cell surface can indeed be used to purify enough HIV-infected tissue cells from infected people for further analysis at the same time, Roan said, "CD127-positive tonsill cells exposed to HIV in vitro provide a new model for studying viral latency in tissues." "
Roan and her team have begun to analyze what makes CD127-positive cells extremely susceptible to latent infections By comparing all the genes expressed in CD127-positive tonsy cells and CD57-positive tonsy cells, they found evidence that CD127-positive tonsy cells were stationary, which may prevent the expression of viral genes In addition, they found that the virus's gene transcription product, RNA, failed to process the necessary virus proteins "Ultimately, we hope that the mechanisms we find can be used to control the latent virus library, bringing us closer to achieving the goal of curing HIV infection," Roan said (biovalleybioon.com) References: 1.FengHsiaoetal.
TissuememoryCD4-Tcellsexpressing IL-7-rett-alpha (CD127) preferentially supportlatentHIVe-1infection
PLoSPres, 2020, doi: 10.1371/journal.ppat.1008450.
2.Scientistsidentifya newpotentialreservoiroflatentHIV
https://medicalxpress.com/news/2020-04-scientists-potential-reservoir-latent-hiv.html