Phosphatidylserine on HIV Envelope Is a Cofactor for Infection of Monocytic Cells

Callahan, Melissa K.; Popernack, Paul M.; Tsutsui, Shigeki; Truong, Linh; Schlegel, Robert; Henderson, Andrew J.

doi:10.4049/jimmunol.170.9.4840

Cited by 126 publications

(124 citation statements)

References 56 publications

(51 reference statements)

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“…By contrast, we propose that TIM-1 accomplishes this task by association of its PS-binding domain located in the IgV domain with the PS exposed on the envelopes of the budding virions. Consistent with this model, PS has been shown to be exposed on the surface of HIV-1 as well as some other viruses (34)(35)(36). Furthermore, we show here that TIM-1 mutants, which are deficient in PS binding, cannot effectively block HIV-1 release, do not induce PS flipping, yet are incorporated into HIV-1 virions.…”

Section: Discussionsupporting

confidence: 67%

“…Viral infection has been shown to induce PS flipping to the outer leaflet of the plasma membrane, accounting for, at least in part, PS exposure on the surface of viral particles (34)(35)(36). We thus examined if expression of TIM-1 induces PS redistribution on the cell membrane, and if so, whether or not this would be important for the TIM-1 inhibition of HIV-1 release.…”

mentioning

confidence: 99%

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TIM-family proteins inhibit HIV-1 release

Ablan

Miao

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

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Significance TIM-family proteins have been recently shown to promote viral entry into host cells. Unexpectedly, we discovered that human TIM-1, along with TIM-3 and TIM-4, potently inhibits HIV-1 release. We showed that TIM-1 is incorporated into HIV-1 virions and retains HIV-1 particles on the plasma membrane via phosphatidylserine (PS), a phospholipid that is exposed on the cellular plasma membrane and the viral envelope. Expression of TIM-1 inhibits HIV-1 replication in CD4 + T cells, and knockdown of TIM-3 in monocyte-derived macrophages enhances HIV-1 production. We extended this function of TIMs to other PS receptors, and demonstrated that they also inhibited release of additional viruses, including murine leukemia virus and Ebola virus. The novel role of TIMs in blocking viral release provides new insights into viral replication and AIDS pathogenesis.

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Section: Discussionsupporting

confidence: 67%

mentioning

confidence: 99%

TIM-family proteins inhibit HIV-1 release

Ablan

Miao

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

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“…In this study, we have shown that the depletion and inhibition of the biosynthesis of cholesterol by treatment with M␤CD and lovastatin, respectively, impaired GP64-dependent internalization but not the binding of the viruses. Phosphatidylserine (PS), which is localized in the inner plasma membrane, is known to be exposed on the envelopes of viral particles of vaccinia virus and HIV (10,46). Morizono et al reported that the serumsoluble protein Gas6 binds to both PS on viral particles and TAM receptor tyrosine kinase Axl on target cells and mediates virus binding by bridging the virus to target cells (52).…”

Section: Discussionmentioning

confidence: 99%

Baculovirus GP64-Mediated Entry into Mammalian Cells

Kataoka

Kaname

Taguwa

et al. 2012

J Virol

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The baculovirus Autographa californica multiple nucleopolyhedrovirus (AcMNPV) serves as an efficient viral vector, not only for abundant gene expression in insect cells, but also for gene delivery into mammalian cells. Lentivirus vectors pseudotyped with the baculovirus envelope glycoprotein GP64 have been shown to acquire more potent gene transduction than those with vesicular stomatitis virus (VSV) envelope glycoprotein G. However, there are conflicting hypotheses about the molecular mechanisms of the entry of AcMNPV. Moreover, the mechanisms of the entry of pseudotyped viruses bearing GP64 into mammalian cells are not well characterized. Determination of the entry mechanisms of AcMNPV and the pseudotyped viruses bearing GP64 is important for future development of viral vectors that can deliver genes into mammalian cells with greater efficiency and specificity. In this study, we generated three pseudotyped VSVs, NPVpv, VSVpv, and MLVpv, bearing envelope proteins of AcMNPV, VSV, and murine leukemia virus, respectively. Depletion of membrane cholesterol by treatment with methyl-␤-cyclodextrin, which removes cholesterol from cellular membranes, inhibited GP64-mediated internalization in a dose-dependent manner but did not inhibit attachment to the cell surface. Treatment of cells with inhibitors or the expression of dominant-negative mutants for dynamin-and clathrin-mediated endocytosis abrogated the internalization of AcMNPV and NPVpv into mammalian cells, whereas inhibition of caveolin-mediated endocytosis did not. Furthermore, inhibition of macropinocytosis reduced GP64-mediated internalization. These results suggest that cholesterol in the plasma membrane, dynamin-and clathrin-dependent endocytosis, and macropinocytosis play crucial roles in the entry of viruses bearing baculovirus GP64 into mammalian cells.

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“…Phosphatidylcholine accounts to 75% of total phospholipid [85] GP Viral envelopes are enriched in sphingomyelin [8,86] SP Envelope cholesterol is critical for structure and infectivity [87][88][89] ST 2 Phosphatidylserine stimulates entry of enveloped viruses [90,91] Mannose receptor binds to the ManLAM mannose caps of mycobacteria and mediates phagocytosis [92] GPI anchored proteins (host [35,36] and parasite [37] …”

Section: Glmentioning

confidence: 99%

Lipidomics of host–pathogen interactions

Wenk

2006

FEBS Letters

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The cell biology of intracellular pathogens (viruses, bacteria, eukaryotic parasites) has provided us with molecular information of host-pathogen interactions. As a result it is becoming increasingly evident that lipids play important roles at various stages of host-pathogen interactions. They act in first line recognition and host cell signaling during pathogen docking, invasion and intracellular trafficking. Lipid metabolism is a housekeeping function in energy homeostasis and biomembrane synthesis during pathogen replication and persistence. Lipids of enormous chemical diversity play roles as immunomodulatory factors. Thus, novel biochemical analytics in combination with cell and molecular biology are a promising recipe for dissecting the roles of lipids in host-pathogen interactions.

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Phosphatidylserine on HIV Envelope Is a Cofactor for Infection of Monocytic Cells

Cited by 126 publications

References 56 publications

TIM-family proteins inhibit HIV-1 release

TIM-family proteins inhibit HIV-1 release

Baculovirus GP64-Mediated Entry into Mammalian Cells

Lipidomics of host–pathogen interactions

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