Highlights of HIV research in April 2021

2021430//---（human immunodeficiency virus, HIV），（AIDS，），

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4，HIV？HIV，

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Use time-lapse fluorescence microscopy to screen the smallest HIV gene circuit for gene expression noise drugs
.
The picture is from PNAS, 2021, doi:10.
1073/pnas.
2012191118
.

8.
Nature Immunology: Defeat HIV-1
doi: 10.
1038/s41590-021-00898-1

CD4+T cell HIV-1 infection with mitochondria as a target triggers the interaction of mitochondrial proteins NLRX1 and FASTKD5 to promote oxidative phosphorylation, leading to Increased virus replication
.
It has now been shown that this process can be blocked by metformin
.
Based on this, Haitao Guo et al.
published a paper entitled "Multi-omics analyses reveal that HIV-1 alters CD4+ T cell immunometabolism to fuel virus replication" in the journal Nature Immunology, which clarified a mechanism leading to the increase of OXPHOS.
And proved that this approach is positively correlated with peak viremia and worse disease outcomes
.
In addition, they have demonstrated that these increases in OXPHOS can be inhibited in human cells and humanized mice with the widely available drug metformin, reducing viremia and T cell depletion in humanized mouse models, indicating that metformin is HIV -1 Possible treatment for infection
.


This study reveals the molecular basis involving NLRX1 and FASTKD5, which can increase the response of OXPHOS to HIV-1 infection
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This promotes viremia and is associated with a poor prognosis of the disease
.
How OXPHOS triggers this effect requires further analysis, as does the exact mechanism by which HIV-1 promotes NLRX1
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The FDA- approved, cheap, safe and widely available type 2 diabetes drug metformin can reduce viremia and viral load by inhibiting OXPHOS
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These findings suggest that targeting OXPHOS with metformin or other mitochondrial inhibitors may help treat HIV-1 infection, combined with antiretroviral therapy
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Targeting this pathway not only reduces peak viremia and viral set points, but also eliminates T cell exhaustion, which is a key complication of HIV-1 infection, as it leads to the progression of AIDS
.
Given the widespread use of metformin in the population, it may be interesting to retrospectively examine whether individuals receiving metformin have reduced viremia and slowed disease progression
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Current research further emphasizes the importance of changes in immune cell metabolism as a driving factor of the disease, in this case AIDS, and heralds innovative treatment methods
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9.
Cell Sub-Journal: Scientists analyze the regulatory mechanism of HIV-1 DNA
doi: 10.
1016/j.
chom.
2021.
03.
001 Professor Paul J Lehner from the Institute of

Therapeutic Immunology and Infectious Diseases of the University of Cambridge leads a team in the Cell sub-Journal " A research paper entitled "The SMC5/6 complex compacts and silences unintegrated HIV-1 DNA and is antagonized by Vpr" was published in the "Cell Host&Microbe" magazine
.


The researchers observed enhanced gene expression from unintegrated HIV-1 DNA in Vpr packaged with viral particles or Vpr delivered by VLP, and it occurred in primary human CD4+ T cells and cell lines
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The raltegravir-independent, Vpr-mediated increase in viral gene expression may also be due to the derepression of the unintegrated genome, because this phenotype is not seen in stably integrated viruses
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In the case of natural infection, the abundance of unintegrated viral DNA species is therefore not just a "dead end" product
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They provide an additional source of viral gene expression, which is enhanced by Vpr
.
At early time points after infection, gene expression from unintegrated viruses can therefore promote the success of the integrated viral genome and form the basis for productive infection, especially if the virus integrates into sites that are not well transcribed
.


The research team’s research describes for the first time a silencing pathway that specifically targets the unintegrated HIV-1 genome
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NP220 dependent silencing and HUSH composite Goff laboratory recently unincorporated MLV retroviral genome linked to raising the apparent display of the research team before genetic silencing complex can inhibit the integration of lentivirus
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However, based on the observations of Goff's laboratory, the research team did not find a role for HUSH complex in silencing unintegrated HIV-1
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Instead, the research team's screening determined the key role of the SLF2 and SMC5/6 complex in silencing the unintegrated lentiviral genome (both HUSH and NP220 are independent)
.

10.
PNAS: CD4 receptor diversity shows the protection mechanism of primate species against immunodeficiency virus
doi: 10.
1073/pnas.
2025914118 Human

and simian immunodeficiency virus (HIV/SIV) infection of the host depends on the viral envelope glycoprotein (Env) binds to the host protein CD4 on the surface of immune cells
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Although this domain is relatively stable in humans, the Env binding domain of chimpanzee CD4 is highly polymorphic: there are 9 different variants in the wild population
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In a recent study published in the journal PNAS, Beatrice H.
Hahn's team from the University of Pennsylvania found that: CD4 diversity is not unique to chimpanzees, and that CD4 receptor diversity is also present in many other African primate species
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A comparative analysis of chimpanzee CD4 sequence diversity and its infection ability, the picture is from PNAS, 2021, doi:10.
1073/pnas.
2025914118
.