LAPTM5 Restricts HIV-1 Infection in Dendritic Cells and Is Counteracted by Vpr

Ouyang, Jiayue; Xiong, Ying; Shang, Hong; Liang, Guoxin

doi:10.1128/spectrum.01382-21

Cited by 8 publications

(5 citation statements)

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“…This gene has been implicated in the activity of the viral protein R (Vpr), which is needed for high viral load and disease progression. Vpr counteracts restriction by LAPTM5 enhance HIV infection in dendritic cells and macrophages 39,40 . LAPTM5 is downregulated in cell lines such Jurkat cells and primary CD4 T cells by Vpr, and this activity could be necessary for HIV replication.…”

Section: Resultsmentioning

confidence: 99%

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Automated microarray platform for single‐cell sorting and collection of lymphocytes following HIV reactivation

Cortés‐Llanos

Jain

Volkheimer

et al. 2023

Bioengineering & Transla Med

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A promising strategy to cure HIV‐infected individuals is to use latency reversing agents (LRAs) to reactivate latent viruses, followed by host clearance of infected reservoir cells. However, reactivation of latent proviruses within infected cells is heterogeneous and often incomplete. This fact limits strategies to cure HIV which may require complete elimination of viable virus from all cellular reservoirs. For this reason, understanding the mechanism(s) of reactivation of HIV within cellular reservoirs is critical to achieve therapeutic success. Methodologies enabling temporal tracking of single cells as they reactivate followed by sorting and molecular analysis of those cells are urgently needed. To this end, microraft arrays were adapted to image T‐lymphocytes expressing mCherry under the control of the HIV long terminal repeat (LTR) promoter, in response to the application of LRAs (prostratin, iBET151, and SAHA). In response to prostratin, iBET151, and SAHA, 30.5%, 11.2%, and 12.1% percentage of cells, respectively. The arrays enabled large numbers of single cells (>25,000) to be imaged over time. mCherry fluorescence quantification identified cell subpopulations with differing reactivation kinetics. Significant heterogeneity was observed at the single‐cell level between different LRAs in terms of time to reactivation, rate of mCherry fluorescence increase upon reactivation, and peak fluorescence attained. In response to prostratin, subpopulations of T lymphocytes with slow and fast reactivation kinetics were identified. Single T‐lymphocytes that were either fast or slow reactivators were sorted, and single‐cell RNA‐sequencing was performed. Different genes associated with inflammation, immune activation, and cellular and viral transcription factors were found.

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Section: Resultsmentioning

confidence: 99%

“…Vpr counteracts restriction by LAPTM5 enhance HIV infection in dendritic cells and macrophages. 39,40 LAPTM5 is downregulated in cell lines such Jurkat cells and primary CD4 T cells by Vpr, and this activity could be necessary for HIV replication.…”

Section: Scrna Sequencing Datamentioning

confidence: 99%

Automated microarray platform for single‐cell sorting and collection of lymphocytes following HIV reactivation

Cortés‐Llanos

Jain

Volkheimer

et al. 2023

Bioengineering & Transla Med

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show abstract

“…While some authors have reported that this Vpr activity was due to an indirect modulating transcriptional effect on the expression of the IFITM3 protein [ 198 ], other authors have suggested that it was related to the modulation of the mannose receptor, a C-type lectin expressed on the cell surface of almost all tissue macrophages, which could also act as an antiviral restriction factor through direct binding to the high-mannose glycan structures of the viral envelope glycoproteins [ 199 , 200 , 201 ]. More recently, a third factor counteracted by Vpr, called LAPTM5 (for lysosomal-associated transmembrane protein 5), that specifically restricts HIV-1 replication in both macrophages and dendritic cells, has been characterized [ 202 , 203 ]. This lysosomal protein might be involved in the inhibition of the late step of the viral envelope trafficking for the optimal infectivity of the released virus particles.…”

Section: Cellular and Molecular Hiv-1 Replication In Macrophagesmentioning

confidence: 99%

Macrophages: Key Cellular Players in HIV Infection and Pathogenesis

Woottum,

Yan,

Sayettat

et al. 2024

Viruses

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Although cells of the myeloid lineages, including tissue macrophages and conventional dendritic cells, were rapidly recognized, in addition to CD4+ T lymphocytes, as target cells of HIV-1, their specific roles in the pathophysiology of infection were initially largely neglected. However, numerous studies performed over the past decade, both in vitro in cell culture systems and in vivo in monkey and humanized mouse animal models, led to growing evidence that macrophages play important direct and indirect roles as HIV-1 target cells and in pathogenesis. It has been recently proposed that macrophages are likely involved in all stages of HIV-1 pathogenesis, including virus transmission and dissemination, but above all, in viral persistence through the establishment, together with latently infected CD4+ T cells, of virus reservoirs in many host tissues, the major obstacle to virus eradication in people living with HIV. Infected macrophages are indeed found, very often as multinucleated giant cells expressing viral antigens, in almost all lymphoid and non-lymphoid tissues of HIV-1-infected patients, where they can probably persist for long period of time. In addition, macrophages also likely participate, directly as HIV-1 targets or indirectly as key regulators of innate immunity and inflammation, in the chronic inflammation and associated clinical disorders observed in people living with HIV, even in patients receiving effective antiretroviral therapy. The main objective of this review is therefore to summarize the recent findings, and also to revisit older data, regarding the critical functions of tissue macrophages in the pathophysiology of HIV-1 infection, both as major HIV-1-infected target cells likely found in almost all tissues, as well as regulators of innate immunity and inflammation during the different stages of HIV-1 pathogenesis.

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“…HIV-1 replicates in monocyte-derived DCs and macrophages; however, this replication is restricted in monocytes ( 39 , 48 ). HIV-1 viral protein binding protein (VprBP) expression is necessary to promote HIV-1 infection.…”

Section: Interplay Between Host Mirnas and Hiv-1mentioning

confidence: 99%

The diverse roles of miRNAs in HIV pathogenesis: Current understanding and future perspectives

et al. 2023

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Despite noteworthy progress made in the management and treatment of HIV/AIDS-related disease, including the introduction of the now almost ubiquitous HAART, there remains much to understand with respect to HIV infection. Although some roles that miRNAs play in some diseases have become more obvious of late, the roles of miRNAs in the context of HIV pathogenesis have not, as yet, been elucidated, and require further investigations. miRNAs can either be beneficial or harmful to the host, depending upon the genes they target. Some miRNAs target the 3′ UTR of viral mRNAs to accomplish restriction of viral infection. However, upon HIV-1 infection, there are several dysregulated host miRNAs which target their respective host factors to either facilitate or abrogate viral infection. In this review, we discuss the miRNAs which play roles in various aspects of viral pathogenesis. We describe in detail the various mechanisms thereby miRNAs either directly or indirectly regulate HIV-1 infection. Moreover, the predictive roles of miRNAs in various aspects of the HIV viral life cycle are also discussed. Contemporary antiretroviral therapeutic drugs have received much attention recently, due to their success in the treatment of HIV/AIDS; therefore, miRNA involvement in various aspects of antiretroviral therapeutics are also elaborated upon herein. The therapeutic potential of miRNAs are discussed, and we also propose herein that the therapeutic potential of one specific miRNA, miR-34a, warrants further exploration, as this miRNA is known to target three host proteins to promote HIV-1 pathogenesis. Finally, future perspectives and some controversy around the expression of miRNAs by HIV-1 are also discussed.

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LAPTM5 Restricts HIV-1 Infection in Dendritic Cells and Is Counteracted by Vpr

Cited by 8 publications

References 5 publications

Automated microarray platform for single‐cell sorting and collection of lymphocytes following HIV reactivation

Automated microarray platform for single‐cell sorting and collection of lymphocytes following HIV reactivation

Macrophages: Key Cellular Players in HIV Infection and Pathogenesis

The diverse roles of miRNAs in HIV pathogenesis: Current understanding and future perspectives

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