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So far, researchers have not been able to accurately quantify a latent form of HIV that persists in patients' immune cells. A new genetic technique is fast and 10 to 100 times more accurate than previous diagnoses.
<img alt = "" clbad = "caption" https: = "" nihgov = "" photos = "" src = "http://www.hhmi.org/sites/default/files/11b_4_hiv_2_715x450.jpg" style = " width: 715px; height: 450px; "title =" This human cell (blue) is attacked by HIV (yellow), the virus that causes AIDS. Even after treatment, the virus continues to hide in the body under a latent form difficult to detect. Seth Pincus, Elizabeth Fischer and Austin Athman; NIAID, NIH. CC BY-NC 2.0"/>
Researchers can now quickly and accurately count a hidden and inactive form of human immunodeficiency virus (HIV) that is hidden in patients' cells. This version of HIV is inscribed in the genome of cells and can persist despite otherwise effective treatments, counteracting attempts to treat the infection.
Using a new genetic technique developed by Robert Siliciano, a researcher at Howard Hughes Medical Institute, and his colleagues, researchers will finally be able to measure how much this viral form is hiding in the body – a crucial element in evaluating the Efficiency of new treatments, says Siliciano.
Previous tools overestimated the number of this form of HIV by 10 to 100 times, potentially masking the significant declines produced by experimental therapies, according to his team's report in the journal. Nature January 30, 2019. "We may still be far from a cure," he says, "but we can at least measure our progress."
<img alt = "" clbad = "caption" src = "http://www.hhmi.org/sites/default/files/hiv4.gif" style = "width: 350px; height: 291px; float: right;" title = "On the HIV envelope (in gray), the proteins (in red) help the virus to bind to and enter host cells Once the virus has entered, it integrates its genetic model into the genome of the host cell. HHMI BioInteractive, Virus Explorer "/> Current HIV treatment uses a combination of antiretroviral drugs, each of which inhibits a specific stage of the life cycle of HIV.When two or more stage blocking drugs are administered simultaneously to a patient, the virus can not replicate and its presence in the blood falls below detection limits, which relieves patients' symptoms and keeps them healthy for decades, but the virus remains in the body, in a latent form difficult to detect, yet less to count: the genetic instructions of the HIV, or model, remain integrated in the system.
HIV exclusively infects immune cells called CD4 cells. A subgroup of these becomes regularly inactive and stores a registry of known infectious agents. Like bright memories, these cells persist indefinitely. But their persistence has a disadvantage: they can, without knowing it, save instructions to make HIV. Once the cells are "awake", these viral models reactivate and become viruses. Thus, HIV-infected patients should stay on antiretroviral treatment forever – unless scientists know how to destroy this so-called "latent reservoir" of HIV.
The first step is to determine the size of the latent reservoir of each patient so that researchers can track their progress while reducing it. But this has been a serious challenge, says Siliciano, an HIV researcher at Johns Hopkins University. When his laboratory members and himself first demonstrated the existence of the latent reservoir in 1995, they did it with the help of a technique developed by them, called Quantitative determination of viral outgrowth (QVOA). The method involves growing HIV-infected cells in the laboratory, which is difficult and takes weeks to complete.
"We may still be far from treatment, but at least we can now measure our progress."
Robert Siliciano
To avoid these problems, most scientists use a simpler technique that relies on a genetic reaction, called PCR, to measure the amount of viral DNA present in CD4 cells. The problem, says Siliciano, is that 98% of HIV information textbooks are so flawed that they are harmless. The method overestimates the number that matters for the health of patients.
The Siliciano team instead devised a PCR reaction that could distinguish defective viral models from intact viruses, using fluorescent probes of two different colors. The probes target areas prone to mutations that can cause defects, and a color reading indicates whether the instructions for HIV are defective or not.
This means that scientists can use the new technique to determine whether a given intervention – an experimental drug or a badtail of drugs, for example – affects the pool of hidden instructions on HIV that really threaten the lives of patients.
"For decades, the field has been demanding a precise measure of these hidden viral patterns," says Siliciano. "Now we have a good way of knowing if we are reducing their numbers."
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Katherine M. Bruner, et al., "A quantitative approach to measuring the reservoir of latent HIV-1 proviruses" Nature. Posted online 30th January 2019. doi: 10.1038 / s41586-019-0898-8
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