HIV envelope gp120 activates human arterial smooth muscle cells

Schecter, Alison D.; Berman, Adriane B.; Yi, Lin; Mosoian, Arevik; McManus, Carrie M.; Berman, Joan W.; Klotman, Mary E.; Taubman, Mark B.

doi:10.1073/pnas.181328798

Cited by 88 publications

(72 citation statements)

References 51 publications

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“…Moreover, other studies have shown that gp120 also induces the MAPK cassette in primary human macrophages 38 and arterial smooth muscle cells. 65 The relevance of all these data remains to be determined, but the ensemble of these reports suggests that multivalent virus-associated gp120 as well as soluble gp120 play a role in the dysregulated physiological responses observed in HIV-1-infected individuals. It is clear that gp120 is not the sole actor in this process, as other HIV-1 regulatory proteins also induce multiple signaling responses.…”

Section: Discussionmentioning

confidence: 99%

gp120-mediated induction of the MAPK cascade is dependent on the activation state of CD4+ lymphocytes

Kinet

Bernard

Mongellaz

et al. 2002

Blood

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The capacity of the HIV-1 envelope glycoprotein gp120 to induce intracellular signals is thought to contribute to HIV-1 pathogenesis. Here, we report that gp120 binding resulted in activation of the mitogen-activated protein kinase (MAPK) in CD4 ؉ lymphocytes prestimulated through their T-cell receptor (TCR). However, gp120 did not activate this pathway in either freshly isolated quiescent T cells or nonproliferating CD4 ؉ lymphocytes prestimulated with the interleukin-7 (IL-7) cytokine. This response was not solely dependent on proliferation per se because proliferating IL-7-prestimulated umbilical cord (UC)-derived T lymphocytes did not exhibit significant MAPK activation upon gp120 binding. Nevertheless, like peripheral blood lymphocytes, MAPK recruitment was induced by gp120 in UC T cells following TCR prestimulation. The lack of a gp120-mediated signaling response was not due to decreased gp120 receptor levels; CD4 expression was modified neither by IL-7 nor by TCR engagement, and high levels of functional CXCR4 were present on IL-7-treated lymphocytes. In addition to CD4 and CXCR4, recent evidence suggests that glycosphingolipids in raft microdomains serve as cofactors for HIV-1 fusion. The ganglioside GM1, a marker of rafts, was augmented in TCR-stimulated but not IL-7-stimulated T lymphocytes, and disruption of rafts inhibited gp120-induced signaling. Thus, stimulation of a mitogenic pathway by gp120 appears to require receptor binding in the context of membrane microdomains. These studies reveal a mechanism via which gp120 may differentially modulate the fate of acti- IntroductionHIV-1 infection is initiated by the fusion of the viral envelope with the cell membrane of the target cell. This process involves the binding of the glycoprotein (gp)120 surface component of the viral envelope glycoproteins with CD4 and either the CXCR4 or CCR5 chemokine coreceptor. [1][2][3][4][5] Thus, the interaction of gp120 with CD4 and a coreceptor is a critical step in HIV-1 infection. However, some of the adverse effects observed in HIV-1-infected individuals are probably not directly related to viral infection. Indeed, one of the hallmarks of AIDS is the depletion of infected as well as uninfected CD4 ϩ T cells, 6,7 raising the question of whether virions and/or viral proteins contribute directly to the pathogenic features of HIV-1.Notably, the interaction of virion-associated gp120 with cell surface CD4 and CXCR4/CCR5 can occur in uninfected cells. Specifically, gp120/gp41 complexes on infected cells may interact with receptor molecules expressed on noninfected cells. Moreover, gp120 proteins shed from both infected cells and HIV-1 virions may bind to uninfected CD4 ϩ cells. 8 A direct role for the HIV-1 envelope glycoprotein in the pathogenesis of the disease has been suggested by studies demonstrating that gp120 can itself transduce intracellular signals. 9 These signals are thought to be mediated via interactions of the HIV-1 envelope with both CD4 and CXCR4/ CCR5 receptors.Binding of stromal cell-derived factor 1...

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Section: Discussionmentioning

confidence: 99%

gp120-mediated induction of the MAPK cascade is dependent on the activation state of CD4+ lymphocytes

Kinet

Bernard

Mongellaz

et al. 2002

Blood

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“…HIV infection itself may increase CV risk. The HIV surface glycoprotein gp120 can stimulate endothelial cell production of tissue factor, an early step in the development of atherosclerosis [188]. Both HIV infection and ART promote atherosclerosis and its clinical manifestations through inflammatory mechanisms involving endothelial cells, either directly or indirectly, and also by inducing lipid alterations [189,190].…”

Section: Clinical Sequelae Associated With Hiv and Hiv-lipodystrophymentioning

confidence: 99%

Lipodystrophy: The Metabolic Link of HIV Infection with Insulin-Resistance Syndrome

Freitas¹,

Carvalho²,

Souto³

et al. 2013

Current Perspectives in HIV Infection

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“…A recent study demonstrated that the HIV envelope protein, gp120, activates human arterial smooth-muscle cells to express tissue factor, the initiator of the coagulation cascade. The activation of smooth muscle cells by gp120 may play an important role in the vascular, thrombotic, and inflammatory responses to HIV infection (89).…”

Section: Infectious Pathogens (I) Helicobacter Pylorimentioning

confidence: 99%

Role of Infectious and Immune Factors in Coronary and Cerebrovascular Arteriosclerosis

Stöllberger

Finsterer

2002

Clin Vaccine Immunol

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HIV envelope gp120 activates human arterial smooth muscle cells

Cited by 88 publications

References 51 publications

gp120-mediated induction of the MAPK cascade is dependent on the activation state of CD4+ lymphocytes

gp120-mediated induction of the MAPK cascade is dependent on the activation state of CD4+ lymphocytes

Lipodystrophy: The Metabolic Link of HIV Infection with Insulin-Resistance Syndrome

Role of Infectious and Immune Factors in Coronary and Cerebrovascular Arteriosclerosis

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