Unbiased Omics Method Finds In Vivo Host Restriction Factors For HIV1
The study, conducted by the Walter Reed Army Institute of Research in Maryland, confirmed the findings of previous studies on host restriction drugs that target HIV-1. In the paper "Monocyte transcription of HIV-1 alpha-prothymazine inhibition in vivo," published in Science Translational Medicine , the authors detail how omics reveal relationships in the search for therapeutic strategies.
Single-cell transcriptomes were used to identify active proteins in cells from 14 HIV-1-infected patients. By correlating a patient's gene expression with the amount of viral RNA (vRNA), the team narrowed down a list of antiviral proteins called host restrictions. These proteins, which are part of the immune system, recognize and intervene at various stages of the virus's replication cycle and thus prevent infection.
The team also compared the sequences of participants with the highest plasma viral load, which showed that the VRNA transcript was associated with PTMA expression of the ProTα gene.
This association was confirmed in 28 other participants outside the original study. Overexpression of prothymazin-α in vitro showed that this cellular factor inhibits HIV-1 replication and production of infectious virus.
Researchers have found that HIV-1 RNA (vRNA) in individual immune cells correlates with several clinical parameters. Using single-cell analysis, the researchers identified vRNA-containing cells in participants during acute HIV infection (AHI) and antiretroviral therapy (ART).
vRNA+ cells are found mainly in CD4+ T cell subsets. Correlation analysis showed that the frequency of vRNA+ CD4+ T cells was positively correlated with such measures as HIV-1 total cellular DNA and viral load in plasma. This indicates that the presence of vRNA in these cells is biologically important and correlates with clinical criteria for HIV-1.
To validate the method, specific restriction of the HIV-1 protease was previously discovered 17 years ago by researchers at Mount Sinai School of Medicine in New York and published in a paper entitled "Prothymosin alpha inhibits expression of viral type 1 immune genes in primary macrophages.” in the journal Prothymosin alpha Virology. .
Previous studies have shown that HIV-1 in human T cells is associated with lower levels of detectable mRNA. The Mount Sinai study showed that protease activity significantly inhibited HIV-1 replication in primary macrophages but did not alter HIV-1 activity in CD4+ T cells.
The present study demonstrates the use of non-invasive omics techniques to identify potential targets of HIV-1 and other viral defenses and therapeutics such as ProTα.
Further information: Aviva Garretts et al. Monocyte transcription determines prothymosin α restriction of HIV-1 in vivo, Scientific Translational Medicine (2023). DOI: 10.1126/scitranslmed.adg0873
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Citation: Omics Unbiased Approach to HIV-1 (2023, August 7) Retrieved August 12, 2023, from https://medicalxpress.com/news/2023-08-unbiased-omics-method-vivo-host Limitation Host in vivo. programming language
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