Role of the Phosphatidylserine Receptor TIM-1 in Enveloped-Virus Entry

Moller-Tank, Sven; Kondratowicz, Andrew S.; Davey, Robert A.; Rennert, Paul D.; Maury, Wendy

doi:10.1128/jvi.01025-13

Cited by 244 publications

(483 citation statements)

References 74 publications

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“…These proteins, either secreted into culture media (Gas6) or expressed on the cell surface (TIMs and TAMs), can interact with PS present on the surface of infectious virions thus enhancing viral entry (8,10,11,39). Here, we have documented a novel function of TIM-family proteins, which inhibits the release of HIV-1, MLV and EBOV from viral producer cells.…”

Section: Discussionmentioning

confidence: 97%

“…There is an increased appreciation that the PS-binding proteins or PS receptors, such as the TIMs, or the Gas6/TAM complex, play important roles in innate sensing and viral infections (8,10,11,(38)(39)(40). These proteins, either secreted into culture media (Gas6) or expressed on the cell surface (TIMs and TAMs), can interact with PS present on the surface of infectious virions thus enhancing viral entry (8,10,11,39).…”

Section: Discussionmentioning

confidence: 99%

“…TIM-1 polymorphisms have been reported to be associated with severe HAV infection in humans (9). More recent studies revealed that TIM-family proteins promote entry of a wide range of viruses, possibly by interacting with virion-associated phosphatidylserine (PS), highlighting a more general role of TIMs in viral infections (10,11).…”

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: Discussionmentioning

confidence: 97%

Section: Discussionmentioning

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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“…84 For example, it has recently been suggested that the Ebola virus can infect epithelial cells through the binding of PS exposed on the viral envelope to the host cell surface PS recognition receptor TIM-1. Although there was no direct evidence for PS-mediated viral internalization, the interaction between PS and TIM-1 was demonstrated to be critical for viral transduction 85,86 (Figure 2f). TIM family receptors and other host-derived phospholipid detectors have also been implicated in PS-mediated uptake of several other viruses including hepatitis A, 87 Lake Victoria marburgvirus, 88 dengue virus 89 and a number of lentiviruses.…”

Section: Pathogenic Entry Via the Host Extracellular Phospholipid Codementioning

confidence: 98%

“…In particular, PS-binding receptors such as BAI-1, RAGE and stablins-1 and -2 have been shown not to support viral infection. 85,89,90 In addition to viruses that demonstrate apoptotic cell mimicry, PS exposure on the viral envelope by vaccinia virus was suggested to allow the virus to mimic an apoptotic body (an intact fragment of an apoptotic cell following cell disassembly), thereby triggering macropinocytosis into the host cell. 91 Interestingly, herpes virus can hijack the host extracellular phospholipid code by hiding inside apoptotic bodies to facilitate their entry into macrophages.…”

Section: Pathogenic Entry Via the Host Extracellular Phospholipid Codementioning

confidence: 99%

The phospholipid code: a key component of dying cell recognition, tumor progression and host–microbe interactions

2015

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A significant effort is made by the cell to maintain certain phospholipids at specific sites. It is well described that proteins involved in intracellular signaling can be targeted to the plasma membrane and organelles through phospholipid-binding domains. Thus, the accumulation of a specific combination of phospholipids, denoted here as the 'phospholipid code', is key in initiating cellular processes. Interestingly, a variety of extracellular proteins and pathogen-derived proteins can also recognize or modify phospholipids to facilitate the recognition of dying cells, tumorigenesis and host-microbe interactions. In this article, we discuss the importance of the phospholipid code in a range of physiological and pathological processes.

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Scramblases and virus infection

et al. 2022

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The asymmetric distribution of lipids, maintained by flippases/floppases and scramblases, plays a pivotal role in various physiologic processes. Scramblases are proteins that move phospholipids between the leaflets of the lipid bilayer of the cellular membrane in an energy-independent manner. Recent studies have indicated that viral infection is closely related to cellular lipid distribution. The level and distribution of phosphatidylserine (PtdSer) in cells have been demonstrated to be critical regulators of viral infections. Previous studies have supported that the infection of human immunodeficiency virus (HIV), Zika virus, Ebola virus (EBOV), influenza virus, and dengue fever virus require the externalization of phospholipids mediated by scramblases, which are also involved in the pathogenicity of the pandemic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). In this review, we review the relationship of scramblases with viruses and the potential viral effector proteins that might utilize host scramblases.

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Role of the Phosphatidylserine Receptor TIM-1 in Enveloped-Virus Entry

Cited by 244 publications

References 74 publications

TIM-family proteins inhibit HIV-1 release

TIM-family proteins inhibit HIV-1 release

The phospholipid code: a key component of dying cell recognition, tumor progression and host–microbe interactions

Scramblases and virus infection

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