HIV-2-Infected Macrophages Produce and Accumulate Poorly Infectious Viral Particles

Gea‐Mallorquí, Ester; Zablocki-Thomas, Laurent; Jouve, Mabel; Rodrigues, Vasco; Ruffin, Nicolas; Benaroch, Philippe

doi:10.3389/fmicb.2020.01603

Cited by 3 publications

(3 citation statements)

References 79 publications

(101 reference statements)

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“…Alternatively, the lack of viral detection in supernatants of exposed cells may reflect a low-level viral replication in Mø and DCs. This lower viral replication is certainly strain-dependent and could be the result of the production of poorly infectious viral particles that accumulate in intracellular structures called virus-containing compartments (VCCs) [ 58 , 59 , 60 ].…”

Section: Discussionmentioning

confidence: 99%

Cell-to-Cell Transmission of HIV-1 and HIV-2 from Infected Macrophages and Dendritic Cells to CD4+ T Lymphocytes

Calado

Pires

Conceição

et al. 2023

Viruses

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Macrophages (Mø) and dendritic cells (DCs) are key players in human immunodeficiency virus (HIV) infection and pathogenesis. They are essential for the spread of HIV to CD4+ T lymphocytes (TCD4+) during acute infection. In addition, they constitute a persistently infected reservoir in which viral production is maintained for long periods of time during chronic infection. Defining how HIV interacts with these cells remains a critical area of research to elucidate the pathogenic mechanisms of acute spread and sustained chronic infection and transmission. To address this issue, we analyzed a panel of phenotypically distinct HIV-1 and HIV-2 primary isolates for the efficiency with which they are transferred from infected DCs or Mø to TCD4+. Our results show that infected Mø and DCs spread the virus to TCD4+ via cell-free viral particles in addition to other alternative pathways. We demonstrate that the production of infectious viral particles is induced by the co-culture of different cell populations, indicating that the contribution of cell signaling driven by cell-to-cell contact is a trigger for viral replication. The results obtained do not correlate with the phenotypic characteristics of the HIV isolates, namely their co-receptor usage, nor do we find significant differences between HIV-1 and HIV-2 in terms of cis- or trans-infection. The data presented here may help to further elucidate the cell-to-cell spread of HIV and its importance in HIV pathogenesis. Ultimately, this knowledge is critical for new therapeutic and vaccine approaches.

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Section: Discussionmentioning

confidence: 99%

Cell-to-Cell Transmission of HIV-1 and HIV-2 from Infected Macrophages and Dendritic Cells to CD4+ T Lymphocytes

Calado

Pires

Conceição

et al. 2023

Viruses

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show abstract

“…HIV-2-infected and HIV-1-infected cells show different metabolic profiles by vpx-mediated SAMHD1 degradation [41]. Another difference between HIV types is that HIV-2 infected macrophages produce poorly infectious HIV particles and they may as such contribute to immune control of HIV-2 [42].…”

Section: Discussionmentioning

confidence: 99%

Monocyte phenotype and extracellular vesicles in HIV-1, HIV-2, and HIV-1/2 dual infection

Hønge

Andersen

Petersen

et al. 2023

Aids

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Objective: AIDS-defining illness develops at higher CD4+ T-cell counts in individuals infected with HIV-2 compared with HIV-1 infected, which suggests that the two types of HIV may have different effects on other compartments of the immune system. We here investigate monocyte phenotype, activation and macrophage-derived extracellular vesicles in individuals with different HIV types. Design: Cross-sectional. Methods: ART-naïve HIV-1 (n = 83), HIV-2 (n = 63), and HIV-1/2 dually-positive (n = 27) participants were recruited in Bissau, Guinea-Bissau, together with HIV-negative controls (n = 26). PBMCs were isolated and analyzed by flow cytometry for monocyte phenotype and activation, and plasma was analyzed for extracellular vesicle forms of CD163 and CD206. Results: Compared with HIV-negative controls, all groups of HIV-positive participants had a skewed monocyte phenotype with a higher proportion of intermediate monocytes, increased CD163 expression, and elevated serum levels of the inflammatory biomarkers soluble (s)CD163 and sCD206. HIV-2-positive participants had lower CD163 monocyte expression than HIV-1-positive participants, regardless of HIV RNA or CD4 cell count. Levels of sCD206 extracellular vesicles were increased in all HIV groups, and higher in HIV-1 compared with HIV-2-positive participants. Conclusion: The monocyte phenotype of HIV-2 positive participants deviated less from healthy controls than did HIV-1 participants. HIV-2 positive participants also had a lower concentration of extracellular CD206+ vesicles compared with HIV-1 positive participants. This does not explain the difference in AIDS development.

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“…Moreover, we found evidence that LAPTM5 can target HIV-2 and the primate lentiviruses SIV mac239 and SIV agm but not MLV and FIV to restrict host infection, raising the possibility that LAPTM5 has a broader role in innate antiviral immunity against primate lentiviruses. Interestingly, HIV-2 infectivity was shown to be much lower than that of HIV-1 when the virus was produced in MDMs 37 , and Gea-Mallorquí et al recently reported that HIV-2 infection of macrophages produces and accumulates poorly infectious viral particles 38 . It is likely that the presence of LAPTM5 is partly responsible for the poorly infectious HIV-2 virions produced in macrophages, given that Vpr of HIV-2 cannot promote degradation of human LAPTM5.…”

Section: Discussionmentioning

confidence: 99%

Vpr counteracts the restriction of LAPTM5 to promote HIV-1 infection in macrophages

Zhao

Wang

et al. 2021

Nat Commun

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The HIV-1 accessory proteins Vif, Vpu, and Nef can promote infection by overcoming the inhibitory effects of the host cell restriction factors APOBEC3G, Tetherin, and SERINC5, respectively. However, how the HIV-1 accessory protein Vpr enhances infection in macrophages but not in CD4+ T cells remains elusive. Here, we report that Vpr counteracts lysosomal-associated transmembrane protein 5 (LAPTM5), a potent inhibitor of HIV-1 particle infectivity, to enhance HIV-1 infection in macrophages. LAPTM5 transports HIV-1 envelope glycoproteins to lysosomes for degradation, thereby inhibiting virion infectivity. Vpr counteracts the restrictive effects of LAPTM5 by triggering its degradation via DCAF1. In the absence of Vpr, the silencing of LAPTM5 precisely phenocopied the effect of Vpr on HIV-1 infection. In contrast, Vpr did not enhance HIV-1 infection in the absence of LAPTM5. Moreover, LAPTM5 was highly expressed in macrophages but not in CD4+ T lymphocytes. Re-expressing LAPTM5 reconstituted the Vpr-dependent promotion of HIV-1 infection in primary CD4+ T cells, as observed in macrophages. Herein, we demonstrate the molecular mechanism used by Vpr to overcome LAPTM5 restriction in macrophages, providing a potential strategy for anti-HIV/AIDS therapeutics.

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HIV-2-Infected Macrophages Produce and Accumulate Poorly Infectious Viral Particles

Cited by 3 publications

References 79 publications

Cell-to-Cell Transmission of HIV-1 and HIV-2 from Infected Macrophages and Dendritic Cells to CD4+ T Lymphocytes

Cell-to-Cell Transmission of HIV-1 and HIV-2 from Infected Macrophages and Dendritic Cells to CD4+ T Lymphocytes

Monocyte phenotype and extracellular vesicles in HIV-1, HIV-2, and HIV-1/2 dual infection

Vpr counteracts the restriction of LAPTM5 to promote HIV-1 infection in macrophages

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