Importance of Membrane Fusion Mediated by Human Immunodeficiency Virus Envelope Glycoproteins for Lysis of Primary CD4-Positive T Cells

LaBonte, Jason A.; Patel, Trushar R.; Hofmann, Wolfgang; Sodroski, Joseph

doi:10.1128/jvi.74.22.10690-10698.2000

Cited by 77 publications

(89 citation statements)

References 52 publications

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“…Studies attempting to correlate an in vitro activity of a particular viral gene product with in vivo pathogenicity have focused on the viral envelope glycoprotein. The fusogenic activity of the envelope glycoprotein contributes both to syncytium-dependent and -independent cell killing (4,30). Whereas destruction of CD4 ϩ T cells in lymph nodes of SHIV-infected monkeys occurred independently of syncytium formation, viruses containing highly fusogenic envelopes were more able to effect lymphocyte depletion (31), which supports a role for envelope glycoprotein in in vivo cytopathogenicity.…”

Section: Discussionmentioning

confidence: 77%

“…Acute cytopathicity is reflected by syncytium formation and syncytiumindependent single cell killing, both of which can be mediated by the fusogenic characteristics of the viral envelope glycoprotein (3)(4)(5). Envelope glycoprotein also mediates virus attachment to receptor and coreceptor molecules on the cell surface, and the ability of HIV-1 strains to induce cytopathic effects in vitro reflects syncytium-inducing and coreceptor usage characteristics of the envelope glycoprotein.…”

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confidence: 99%

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Evidence for a cytopathogenicity determinant in HIV-1 Vpr

Somasundaran

Sharkey

Břicháček

et al. 2002

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

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HIV-1 is cytopathic for CD4 ؉ T lymphocytes in vitro and this property of HIV-1 is generally considered to account for some of its in vivo cytopathogenicity. Thus, the extent of lymphocyte depletion correlates with the level of viremia whereas low levels of viral replication are typically associated with stable lymphocyte levels and asymptomatic infection such as is observed in non-progressors. Here, we describe a non-progressor who did not fit this general pattern in that CD4 ؉ T lymphocyte homeostasis was maintained in the face of high-level viral replication. Biological viral isolates from this patient replicated in primary lymphocytes without inducing cytopathicity. Because this phenotype is reminiscent of Vpr-deleted viruses, we examined the contribution of the Vpr gene to the viral phenotype. Vpr alleles derived from this patient contained both premature stop codons and an unusual Q3R polymorphism. Insertion of patientderived Vpr alleles or a Q3R substitution into a cytopathic HIV-1 clone resulted in a marked impairment of cytopathicity without affecting viral replication efficiency. The effect of Vpr on cytopathicity was unrelated to reported activities of Vpr including virion association, interaction with uracil DNA glycosylase, G 2 arrest, or enhancement of macrophage infection but correlated with the ability of Vpr to induce host cell apoptosis. This study suggests the presence of a determinant of in vivo cytopathogenicity within HIV-1 Vpr and further indicates that viral replication can be uncoupled from cytopathicity in vitro and in vivo.

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Section: Discussionmentioning

confidence: 77%

mentioning

confidence: 99%

Evidence for a cytopathogenicity determinant in HIV-1 Vpr

Somasundaran

Sharkey

Břicháček

et al. 2002

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

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“…Additionally, deletion of env coding sequences from pTRG would avoid the toxic effects associated with env expression. 48 To increase efficacy, the incorporation of ribozymes and a mutant RRE that is not sensitive to TdRev 49 would allow construction of vectors with higher titers and higher inhibitory potential.…”

Section: Figure 9 Infectivity Of Virions Released From Supt1/trg and mentioning

confidence: 99%

“…The calcium phosphate DNA coprecipitation method was used to transfect a total of 25 g of plasmid DNA per dish: 8 g of transfer vector plasmid, 8 g of the packaging helper plasmid pCMV⌬R8.2, 4 g of pLTR-G and 5 g of pCMVRev. After 16 h, cells were washed three times with PBS, 10 ml of new medium was added and cells were incubated for another 48 …”

Section: Hiv-1 Inhibition By Transient Transfection Assaymentioning

confidence: 99%

Inhibition of HIV-1 replication by novel lentiviral vectors expressing transdominant Rev and HIV-1 env antisense

2002

Gene Ther

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“…HIV-1 induces the fusion of uninfected CD4 ϩ CXCR4/CCR5 ϩ cells and infected cells expressing Env, resulting in the formation of giant multinucleated cells, termed syncytia. Cell-to-cell fusion represents another way of virus spreading with the advantage of being inaccessible to humoral immune response (7)(8)(9)(10). Moreover, viral strains prone to induce syncytia usually emerged simultaneously with the entry into AIDS phase (11).…”

mentioning

confidence: 99%

Tetraspanins CD9 and CD81 Modulate HIV-1-Induced Membrane Fusion

Gordon-Alonso

Yáñez-Mó

Barreiro

et al. 2006

The Journal of Immunology

152

141

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Protein organization on the membrane of target cells may modulate HIV-1 transmission. Since the tetraspanin CD81 is associated to CD4, the receptor of HIV-1 envelope protein (Env; gp120/gp41), we have explored the possibility that this molecule may modulate the initial steps of HIV-1 infection. On the other hand, CD81 belongs to the tetraspanin family, which has been described as organizers of protein microdomains on the plasma membrane. Therefore, the role of CD81 and other related tetraspanin, CD9, on the cell-to-cell fusion process mediated by HIV-1 was studied. We found that anti-tetraspanin Abs enhanced the syncytia formation induced by HIV-1 envelope proteins and viral entry in human T lymphoblasts. In addition, anti-CD81 Abs triggered its clustering in patches, where CD4 and CXCR4 were included. Moreover, the knocking down of CD81 and CD9 expression resulted in an increase in syncytia formation and viral entry. Accordingly, overexpression of CD81 and CD9 rendered cells less susceptible to Env-mediated syncytia formation. These data indicate that CD9 and CD81 have an important role in membrane fusion induced by HIV-1 envelope.

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Importance of Membrane Fusion Mediated by Human Immunodeficiency Virus Envelope Glycoproteins for Lysis of Primary CD4-Positive T Cells

Abstract: In established T-cell lines, the membrane-fusing capacity of the human immunodeficiency virus type 1 (HIV-1) envelope glycoproteins mediates cytopathic effects, both syncytium formation and single-cell lysis.

Cited by 77 publications

References 52 publications

Evidence for a cytopathogenicity determinant in HIV-1 Vpr

Evidence for a cytopathogenicity determinant in HIV-1 Vpr

Inhibition of HIV-1 replication by novel lentiviral vectors expressing transdominant Rev and HIV-1 env antisense

Tetraspanins CD9 and CD81 Modulate HIV-1-Induced Membrane Fusion

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