The differential expression of CREM/ICER subtypes is related to the spontaneous control of HIV infection

A rare type of HIV-infected people, called elite controllers (ECs), can maintain long-term control of HIV replication in the absence of antiretroviral therapy (ART)

In order to clarify the biological mechanism of resistance to HIV replication at the molecular and cellular levels, we performed RNA sequencing and identified selectivity among ECs, HIV-infected individuals receiving ART, HIV-infected individuals without ART treatment, and healthy controls.

A small group of HIV-infected people called elite controllers (ECs) showed control of HIV replication without antiretroviral therapy (ART)

1) This is contrary to the situation of most people, among these people, unless they receive antiretroviral therapy, HIV infection will progress to AIDS

Several host restriction factors have been identified as inhibiting viral replication

⁺T cells of HIV controllers are less susceptible to HIV infectionin vitro(11,12) However, the limitation of virus replication in CD4⁺T cells from HIV controllers can be overcome by high-dose viral challenges (11,13) In addition, some reports found that CD4⁺T cells from ECs can be infected by HIV strains from themselves or in the laboratory (13,14A previous study identified potential host factors that regulate viral replication in CD4 transcripts⁺Comparison of endothelial cells and T cells in patients with simple anti-retroviral infection (15) Although the transcription profile has a broad correlation with the viral set point of the patient, it is not clear whether this profile is caused by different levels of infected T cells in the sample or by system differences within the individual

Since monocytes are not the main target of infection, sequencing the monocyte population will further avoid confounding factors caused by infection-dependent changes
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To test this hypothesis, we performed transcriptomics analysis to analyze the gene expression profiles of monocytes from ECs, HIV-infected individuals receiving ART, HIV-infected individuals without ART infection, and healthy controls
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We focused on the genes whose expression of ECs increased or decreased compared with the other three control groups (non-ECs)
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Here, we found that in endothelial cells, ICER (inducible early inhibitor of cyclic AMP [cAMP]) site-specific exon expression increased
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Methamphetamine gene knockout in CD4⁺T cell lines increase HIV infection;Overexpression or knockout of these subtypes in primary CD4⁺T cells reduce or increase HIV infection, respectively
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These findings indicate that specific genetic programs in ECs, including altering the splicing of ICER, may modulate cell resistance to HIV infection
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