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Virus World provides a daily blog of the latest news in the Virology field and the COVID-19 pandemic. News on new antiviral drugs, vaccines, diagnostic tests, viral outbreaks, novel viruses and milestone discoveries are curated by expert virologists. Highlighted news include trending and most cited scientific articles in these fields with links to the original publications. Stay up-to-date with the most exciting discoveries in the virus world and the last therapies for COVID-19 without spending hours browsing news and scientific publications. Additional comments by experts on the topics are available in Linkedin (https://www.linkedin.com/in/juanlama/detail/recent-activity/)
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HIV Silencing and Cell Survival Signatures in Infected T Cell Reservoirs - Nature

HIV Silencing and Cell Survival Signatures in Infected T Cell Reservoirs - Nature | Virus World | Scoop.it

Rare CD4 T cells that contain HIV under antiretroviral therapy represent an important barrier to HIV cure1–3, but the infeasibility of isolating and characterizing these cells in their natural state has led to uncertainty about whether they possess distinctive attributes that HIV cure-directed therapies might exploit. Here we address this challenge using a microfluidic technology that isolates the transcriptomes of HIV-infected cells based solely on the detection of HIV DNA. HIV-DNA+ memory CD4 T cells in the blood from people receiving antiretroviral therapy showed inhibition of six transcriptomic pathways, including death receptor signalling, necroptosis signalling and antiproliferative Gα12/13 signalling. Moreover, two groups of genes identified by network co-expression analysis were significantly associated with HIV-DNA+ cells. These genes (n = 145) accounted for just 0.81% of the measured transcriptome and included negative regulators of HIV transcription that were higher in HIV-DNA+ cells, positive regulators of HIV transcription that were lower in HIV-DNA+ cells, and other genes involved in RNA processing, negative regulation of mRNA translation, and regulation of cell state and fate. These findings reveal that HIV-infected memory CD4 T cells under antiretroviral therapy are a distinctive population with host gene expression patterns that favour HIV silencing, cell survival and cell proliferation, with important implications for the development of HIV cure strategies. HIV-infected memory CD4 T cells under antiretroviral therapy are a distinctive population of cells with transcriptomic patterns that favour HIV silencing, cell survival and cell proliferation.

 

Published in Nature (Jan. 4, 2023):

https://doi.org/10.1038/s41586-022-05556-6 

Antoine Godard's curator insight, January 16, 2023 7:20 AM
Grâce à une technologie microfluidique qui isole les transcriptomes des cellules infectées par le VIH, ces scientifiques ont réussi isoler et caractériser les cellules T CD4 rares qui contiennent le VIH sous traitement antirétroviral pour savoir si elles possèdent des attributs distinctifs que les thérapies dirigées par la guérison du VIH pourraient exploiter. Cette étude a montré une inhibition de six voies transcriptomiques et deux groupes de gènes significativement associés aux cellules VIH-ADN. Ces découvertes pourraient servir à l’élaboration d’un vaccin.
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In a First, a Person’s Immune System Fought HIV — and Won

In a First, a Person’s Immune System Fought HIV — and Won | Virus World | Scoop.it

Some rare people may purge most HIV from their bodies, leaving only broken copies of the virus or copies locked in molecular prisons, from which there is no escape. Twice, people infected with HIV have had levels of the virus in their bodies drop to undetectable levels after bone marrow transplants, never to return (SN: 3/5/19). Now it appears that a person may have cleared functional HIV with no outside help. If true, it would be the first known instance of a spontaneous cure. Analysis of more than 1.5 billion cells taken from a patient known as EC2 showed no functional HIV copies in any of them, researchers report August 26 in Nature. The person still had some nonfunctional copies of the virus. While no one can say for sure that intact virus isn’t hiding in a cell somewhere in this person’s body, the finding suggests that some people’s immune systems can get the upper hand, essentially eliminating the pernicious and persistent virus. A second person, EC1, had just one functional copy of HIV in more than 1 billion blood cells analyzed. And that copy of HIV was stuck in what is essentially a genetic supermax prison. That genetic lockup may be key to being able to naturally control the virus. Those two people are part of a rare group of people known as elite controllers, meaning they are able to maintain very low or undetectable levels of HIV without antiretroviral drugs. These people have no symptoms or clear signs of damage from the virus. “It’s not even that we’re talking about a few months or a few years. It’s extremely long-term,” says Satya Dandekar, an HIV researcher at the University of California, Davis School of Medicine who was not involved in the study. In contrast, for 99.5 percent or more of the world’s 35 million people infected with the virus, drugs are the only way to keep the virus down.

 

Researchers want to know how elite controllers quash the virus for long periods of time. It has been difficult to figure it out, Dandekar says, because no one has recorded the first fight scenes between HIV and the elite controllers’ immune systems. “We miss the initial punches the immune system has thrown at the virus.” And by the time anyone recognizes an elite controller, the fight is already won. About a quarter of elite controllers have genetic variants in key immune system genes that may help them get a handle on the virus, says Joseph Wong, a virologist at the University of California, San Francisco. But that explains what’s going on in only a minority of elite controllers, and isn’t something easily transferred to others, he says. It’s possible that the elite controllers were infected with “wimpy” versions of HIV, Dandekar says. So the researchers examined the HIV viruses embedded in DNA from 64 elite controllers and 41 HIV-infected people taking antiretroviral drugs. The elite controllers had maintained undetectable levels of virus without drugs from one to, in EC2’s case, 24 years. The median was nine years. HIV is a retrovirus, which means that it stores its genetic information as RNA. An enzyme called reverse transcriptase copies those RNA instructions into DNA, which can then insert into the host’s DNA. Reverse transcriptase is error prone, often resulting in defective or incomplete copies of the virus. So the researchers went into the study thinking that elite controllers might be loaded with these nonfunctional versions, which can’t make infectious virus, says Xu Yu, an immunologist at the Ragon Institute of MGH, MIT and Harvard in Boston. “But to our surprise, that’s not the case,” she says. Instead, most elite controllers in the study have more intact virus than expected. So Yu and colleagues looked to see where the virus had landed in patients’ DNA....

 

Published in Nature (August 26, 2020):

https://doi.org/10.1038/s41586-020-2651-8

good health's curator insight, January 10, 10:33 AM

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