Attachment of human immunodeficiency virus to cells and its inhibition

Pöhlmann, Stefan; Tremblay, Michel J.

doi:10.1007/978-3-7643-7783-0_3

Cited by 4 publications

(2 citation statements)

References 128 publications

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“…Incorporation of host cell factors into the HIV envelope can also increase viral infectivity. The augmentation of infectivity is due to the interaction of the virion-incorporated factors with their cognate receptors on HIV target cells, as exemplified by the up to 100-fold increased infectivity of ICAM-1-bearing viruses for LFA-1 positive target cells [ 12 , 13 ]. Finally, attachment of HIV to dendritic cells can also promote HIV infection of adjacent T-cells [ 14 , 15 ], and this property has been associated with the expression of DC-SIGN [ 16 ], a calcium-dependent (C-type) lectin which recognizes mannose-rich carbohydrates on the HIV Env protein [ 17 - 19 ].…”

Section: Introductionmentioning

confidence: 99%

Incorporation of podoplanin into HIV released from HEK-293T cells, but not PBMC, is required for efficient binding to the attachment factor CLEC-2

et al. 2010

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BackgroundPlatelets are associated with HIV in the blood of infected individuals and might modulate viral dissemination, particularly if the virus is directly transmitted into the bloodstream. The C-type lectin DC-SIGN and the novel HIV attachment factor CLEC-2 are expressed by platelets and facilitate HIV transmission from platelets to T-cells. Here, we studied the molecular mechanisms behind CLEC-2-mediated HIV-1 transmission.ResultsBinding studies with soluble proteins indicated that CLEC-2, in contrast to DC-SIGN, does not recognize the viral envelope protein, but a cellular factor expressed on kidney-derived 293T cells. Subsequent analyses revealed that the cellular mucin-like membranous glycoprotein podoplanin, a CLEC-2 ligand, was expressed on 293T cells and incorporated into virions released from these cells. Knock-down of podoplanin in 293T cells by shRNA showed that virion incorporation of podoplanin was required for efficient CLEC-2-dependent HIV-1 interactions with cell lines and platelets. Flow cytometry revealed no evidence for podoplanin expression on viable T-cells and peripheral blood mononuclear cells (PBMC). Podoplanin was also not detected on HIV-1 infected T-cells. However, apoptotic bystander cells in HIV-1 infected cultures reacted with anti-podoplanin antibodies, and similar results were obtained upon induction of apoptosis in a cell line and in PBMCs suggesting an unexpected link between apoptosis and podoplanin expression. Despite the absence of detectable podoplanin expression, HIV-1 produced in PBMC was transmitted to T-cells in a CLEC-2-dependent manner, indicating that T-cells might express an as yet unidentified CLEC-2 ligand.ConclusionsVirion incorporation of podoplanin mediates CLEC-2 interactions of HIV-1 derived from 293T cells, while incorporation of a different cellular factor seems to be responsible for CLEC-2-dependent capture of PBMC-derived viruses. Furthermore, evidence was obtained that podoplanin expression is connected to apoptosis, a finding that deserves further investigation.

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Section: Introductionmentioning

confidence: 99%

Incorporation of podoplanin into HIV released from HEK-293T cells, but not PBMC, is required for efficient binding to the attachment factor CLEC-2

et al. 2010

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“…1). One of the best studied examples is the incorporation of cellular ICAM-1 into the HIV envelope and its interaction with LFA-1 on the surface of target cells (Pöhlmann and Tremblay 2007), which is in the focus of the present discussion.…”

Section: Host Cell Factors Incorporated Into the Viral Envelopementioning

confidence: 99%

Attachment/Binding

Karsten¹,

Pöhlmann²

2013

Encyclopedia of AIDS

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DefinitionThe envelope glycoprotein (Env) of the human immunodeficiency virus (HIV) mediates entry into target cells. Binding of Env to cellular attachment-promoting factors (attachment factors) is frequently unspecific and generally dispensable for entry. However, engagement of attachment factors can profoundly augment HIV infectivity and might impact viral tropism and spread. The lectin DC-SIGN is an archetypic attachment factor, which can facilitate capture of infectious HIV by dendritic cells and might impact HIV transmission and dissemination.

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Attachment/Binding

Karsten¹,

Pöhlmann²

2018

Encyclopedia of AIDS

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Attachment of human immunodeficiency virus to cells and its inhibition

Cited by 4 publications

References 128 publications

Incorporation of podoplanin into HIV released from HEK-293T cells, but not PBMC, is required for efficient binding to the attachment factor CLEC-2

Incorporation of podoplanin into HIV released from HEK-293T cells, but not PBMC, is required for efficient binding to the attachment factor CLEC-2

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Attachment/Binding

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