Alterations in Cholesterol Metabolism Restrict HIV-1 
            <i>Trans</i>
            Infection in Nonprogressors

Rappocciolo, Giovanna; Jais, Mariel; Piazza, Paolo; Reinhart, Todd A.; Berendam, Stella J.; García-Expósito, Laura; Gupta, Phalguni; Rinaldo, Charles R.

doi:10.1128/mbio.01031-13

Cited by 33 publications

(63 citation statements)

References 38 publications

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“…This deficiency was mapped to increased expression of the reverse cholesterol transporter, ABCA1, in DCs resulting in reduced cellular levels of cholesterol [120]. These in vivo findings nicely corroborate previous in vitro observations that demonstrated robust decreases in HIV-1 capture and trans infection by DCs upon cholesterol depletion [121,122].…”

Section: Ongoing Challenges: In Vivosupporting

confidence: 83%

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A Mechanistic Overview of Dendritic Cell-Mediated HIV-1 Trans Infection: The Story So Far

Kijewski

Gummuluru

2015

Future Virol.

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Despite progress in antiretroviral therapy, HIV-1 rebound after cessation of antiretroviral therapy suggests that establishment of long-term cellular reservoirs of virus is a significant barrier to functional cure. There is considerable evidence that dendritic cells (DCs) play an important role in systemic virus dissemination. Although productive infection of DCs is inefficient, DCs capture HIV-1 and transfer-captured particles to CD4+ T cells, a mechanism of DC-mediated HIV-1 trans infection. Recent findings suggest that DC-mediated trans infection of HIV-1 is dependent on recognition of GM3, a virus-particle-associated host-derived ligand, by CD169 expressed on DCs. In this review, we describe mechanisms of DC-mediated HIV-1 trans infection and discuss specifically the role of CD169 in establishing infection in CD4+ T cells.

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Section: Ongoing Challenges: In Vivosupporting

confidence: 83%

“…Interestingly, in a recently published clinical study, DCs from HIV-1 infected nonprogressors were unable to mediate HIV-1 trans infection of CD4 + T cells [120]. This deficiency was mapped to increased expression of the reverse cholesterol transporter, ABCA1, in DCs resulting in reduced cellular levels of cholesterol [120].…”

Section: Ongoing Challenges: In Vivomentioning

confidence: 99%

A Mechanistic Overview of Dendritic Cell-Mediated HIV-1 Trans Infection: The Story So Far

Kijewski

Gummuluru

2015

Future Virol.

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“…Moreover, plaque sizes were partially restored upon addition of exogenous cholesterol, suggesting that cell-to-cell spread of HSV-1 is cholesterol dependent. Cell cholesterol modulation has been proposed to limit the progression of HIV infection in a subset of the infected population (44,45). In nonprogressors, a reduction in cell cholesterol inhibited the ability of HIV-infected antigen-presenting cells to trans-infect susceptible T cells by interfering with the formation of a virological synapse (44,45).…”

Section: Discussionmentioning

confidence: 99%

Cellular Cholesterol Facilitates the Postentry Replication Cycle of Herpes Simplex Virus 1

Wudiri

Nicola

2017

J Virol

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Cholesterol is an essential component of cell membranes and is required for herpes simplex virus 1 (HSV-1) entry (1-3). Treatment of HSV-1-infected Vero cells with methyl beta-cyclodextrin from 2 to 9 h postentry reduced plaque numbers. Transport of incoming viral capsids to the nuclear periphery was unaffected by the cholesterol reduction, suggesting that cell cholesterol is important for the HSV-1 replicative cycle at a stage(s) beyond entry, after the arrival of capsids at the nucleus. The synthesis and release of infectious HSV-1 and cell-to-cell spread of infection were all impaired in cholesterol-reduced cells. Propagation of HSV-1 on DHCR24 Ϫ/Ϫ fibroblasts, which lack the desmosterol-to-cholesterol conversion enzyme, resulted in the generation of infectious extracellular virions (HSV des ) that lack cholesterol and likely contain desmosterol. The specific infectivities (PFU per viral genome) of HSV chol and HSV des were similar, suggesting cholesterol and desmosterol in the HSV envelope support similar levels of infectivity. However, infected DHCR24 Ϫ/Ϫ fibroblasts released ϳ1 log less infectious HSV des and ϳ1.5 log fewer particles than release of cholesterol-containing particles (HSV chol ) from parental fibroblasts, suggesting that the hydrocarbon tail of cholesterol facilitates viral synthesis. Together, the results suggest multiple roles for cholesterol in the HSV-1 replicative cycle.IMPORTANCE HSV-1 infections are associated with a wide range of clinical manifestations that are of public health importance. Cholesterol is a key player in the complex interaction between viral and cellular factors that allows HSV-1 to enter host cells and establish infection. Previous reports have demonstrated a role for cellular cholesterol in the entry of HSV-1 into target cells. Here, we employed both chemical treatment and cells that were genetically defined to synthesize only desmosterol to demonstrate that cholesterol is important at stages following the initial entry and transport of viral capsids to the nucleus. Viral protein expression, encapsidation of the viral genome, and the release of mature virions were impacted by the reduction of cellular cholesterol. Cholesterol was also critical for cell-to-cell spread of infection. These findings provide new insights into the cholesterol dependence of HSV-1 replication.KEYWORDS cholesterol, herpes simplex virus, herpesviruses, sterols T he entry of several herpesviruses into target cells requires cell membrane cholesterol (1-6). Membrane cholesterol is essential for maintaining membrane order, reducing permeability, and a host of other cellular functions, including cell signaling (7-10). Entry of the alphaherpesviruses herpes simplex virus 1 (HSV-1) and pseudorabies virus requires target membrane cholesterol at the fusion step (1, 3), but not for virus attachment to cells (2, 6). Herpesviruses utilize low-pH endosomal entry pathways and pH-independent routes, both of which require cholesterol (11-13). Membrane cholesterol plays a general role in viral entry...

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“…Certain viruses, including HIV-1, utilize the organized lipid raft structure at the T cell plasma membrane for entry and assembly, with both processes requiring the presence of cholesterol [55]. In support of this, the cholesterol content of the plasma membrane of dendritic cells, B cells and macrophages in HIV-1 non-progressors is reduced compared to rapid progressors, with the cholesterol content of the cell correlating with the capacity of HIV-1 to undergo cell-to-cell spread [56,57].…”

Section: Fatty Acid and Lipid Metabolismmentioning

confidence: 97%

T cell metabolism in chronic viral infection

Pallett

Schmidt

Schurich

2019

Clinical and Experimental Immunology

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T cells are a fundamental component of the adaptive immune response in the context of both acute and chronic viral infection. Tight control over the metabolic processes within T cells provides an additional level of immune regulation that is interlinked with nutrient sensing and the continued balancing of co-stimulatory and co-inhibitory signals. Underpinning T cell responsiveness for viral control are a number of phenotypic and functional adaptations ensuring adequate nutrient uptake and their utilization. T cells responding to persistent viral infections often exhibit a profile associated with immune cell exhaustion and a dysregulated metabolic profile, driven by a combination of chronic antigenic stimulation and signals from the local microenvironment. Understanding alterations in these metabolic processes provides an important basis for immunotherapeutic strategies to treat persistent infections. T cell metabolism in chronic viral infection OTHER ARTICLES PUBLISHED IN THIS REVIEW SERIESTranslating immunometabolism: towards curing human diseases by targeting metabolic processes underpinning the immune response. Clinical and Experimental Immunology 2019, 197: 141-142. Sculpting tumor microenvironment with immune system: from immunometabolism to immunoediting. Clinical and Experimental Immunology 2019, 197: 153-160. Sensing between reactions -how the metabolic microenvironment shapes immunity. Clinical and Experimental Immunology 2019, 197: 161-169. Altered metabolic pathways regulate synovial inflammation in rheumatoid arthritis.

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Alterations in Cholesterol Metabolism Restrict HIV-1 Trans Infection in Nonprogressors

Cited by 33 publications

References 38 publications

A Mechanistic Overview of Dendritic Cell-Mediated HIV-1 Trans Infection: The Story So Far

A Mechanistic Overview of Dendritic Cell-Mediated HIV-1 Trans Infection: The Story So Far

Cellular Cholesterol Facilitates the Postentry Replication Cycle of Herpes Simplex Virus 1

T cell metabolism in chronic viral infection

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