Human CD38 interferes with HIV‐1 fusion through a sequence homologous to the V3 loop of the viral envelope glycoprotein gp120.

Savarino, Andrea; Bensi, Thea; Chiocchetti, Annalisa; Bottarel, Flavia; Mesturini, Riccardo; Ferrero, Enza; Calosso, Liliana; Deaglio, Silvia; Ortolan, Erika; Buttò, Stefano; Cafaro, Aurelio; Katada, Toshiaki; Ensoli, Barbara; Malavasi, Fabio; Dianzani, Umberto

doi:10.1096/fj.02-0512fje

Cited by 28 publications

(24 citation statements)

References 56 publications

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“…Indeed, CD38 expression partially prevents HIV-1 infection due to the homology between the membrane proximal domain of CD38 and a distinct region of the gp120 HIV-1 envelope protein. 39 The results of the present study may fit the model, indicating that CD38/CXCR4 physiological interactions account for reduced accessibility of CXCR4 to HIV-1, thus limiting infection.…”

Section: Discussionsupporting

confidence: 56%

CD38 increases CXCL12-mediated signals and homing of chronic lymphocytic leukemia cells

et al. 2010

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Homing of chronic lymphocytic leukemia (CLL) cells to sites favoring growth, a critical step in disease progression, is principally coordinated by the CXCL12/CXCR4 axis. A cohort of 62 CLL patients was divided into migrating and nonmigrating subsets according to chemotaxis toward CXCL12. Migrating patients phosphorylated extracellular signal-regulated kinase 1/2 (ERK1/2) proteins more than nonmigrating patients (Po0.0002). CD38 expression was the parameter most strongly associated with heightened CXCL12 signaling (Po0.0001), confirmed by independent statistical approaches. Consistent with this observation, CD38À CLL cells in samples with bimodal CD38 expression responded less to CXCL12 than the intact clone (P ¼ 0.003). Furthermore, lentivirus-induced de novo expression of CD38 was paralleled by increased responses to CXCL12, as compared with cells infected with a control virus. CD38 ligation with agonistic monoclonal antibodies (mAbs) enhanced CXCL12 signaling, whereas blocking anti-CD38 mAbs inhibited chemokine effects in vitro. This is attributed to physical proximity on the membrane between CD38 and CXCR4 (the CXCL12 receptor), as shown by (i) coimmunoprecipitation and (ii) confocal microscopy experiments. Blocking anti-CD38 mAbs significantly compromised homing of CLL cells from blood to lymphoid organs in a mouse model. These results indicate that CD38 synergizes with the CXCR4 pathway and support the working hypothesis that migration is a central step in disease progression.

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Section: Discussionsupporting

confidence: 56%

CD38 increases CXCL12-mediated signals and homing of chronic lymphocytic leukemia cells

et al. 2010

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“…Although its enzymatic activities and signaling pathway are understood in some detail, the true biologic function exerted in vivo by CD38 remains elusive. Interest in the molecule was refueled by independent reports of its involvement in a heterogeneous number of human diseases, which include HIV infection, 30 diabetes, prostatic carcinoma, acute promyelocytic leukemia, 12 and, most recently, B-CLL. The results of the lateral association experiments between CD79␣ and CD81, CD79␤ and CD81, IgM and CD81, and IgD and CD81, are summarized.…”

Section: Discussionmentioning

confidence: 99%

CD38 is a signaling molecule in B-cell chronic lymphocytic leukemia cells

Deaglio

Capobianco

Bergui

et al. 2003

Blood

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165

152

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The prognosis for patients with B-cell chronic lymphocytic leukemia (B-CLL) is generally less favorable for those expressing CD38. Our working hypothesis is that CD38 is not merely a marker in B-CLL, but that it plays a receptor role with pathogenetic potential ruling the proliferation of the malignant clone. CD38 levels were generally low in the patients examined and monoclonal antibody (mAb) ligation was inefficient in signaling. Other cellular models indicated that molecular density and surface organization are critical for CD38 functionality. Interleukin 2 (IL-2) induced a marked up-modulation and surface rearrangement of CD38 in all the patients studied. On reaching a specific expression threshold, CD38 becomes an efficient receptor in purified B-CLL cells. Indeed, mAb ligation is followed by

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“…The membrane proximal domain is involved in binding the HIV coat protein gp120, resulting in a modulation of viral entry into the target cell (303). This region is also thought to be the one interacting with CD31 (U.…”

Section: A Cd38mentioning

confidence: 99%

Evolution and Function of the ADP Ribosyl Cyclase/CD38 Gene Family in Physiology and Pathology

Malavasi¹,

Deaglio²,

Funaro³

et al. 2008

Physiological Reviews

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747

794

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The membrane proteins CD38 and CD157 belong to an evolutionarily conserved family of enzymes that play crucial roles in human physiology. Expressed in distinct patterns in most tissues, CD38 (and CD157) cleaves NAD(+) and NADP(+), generating cyclic ADP ribose (cADPR), NAADP, and ADPR. These reaction products are essential for the regulation of intracellular Ca(2+), the most ancient and universal cell signaling system. The entire family of enzymes controls complex processes, including egg fertilization, cell activation and proliferation, muscle contraction, hormone secretion, and immune responses. Over the course of evolution, the molecules have developed the ability to interact laterally and frontally with other surface proteins and have acquired receptor-like features. As detailed in this review, the loss of CD38 function is associated with impaired immune responses, metabolic disturbances, and behavioral modifications in mice. CD38 is a powerful disease marker for human leukemias and myelomas, is directly involved in the pathogenesis and outcome of human immunodeficiency virus infection and chronic lymphocytic leukemia, and controls insulin release and the development of diabetes. Here, the data concerning diseases are examined in view of potential clinical applications in diagnosis, prognosis, and therapy. The concluding remarks try to frame all of the currently available information within a unified working model that takes into account both the enzymatic and receptorial functions of the molecules.

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Human CD38 interferes with HIV‐1 fusion through a sequence homologous to the V3 loop of the viral envelope glycoprotein gp120.

Cited by 28 publications

References 56 publications

CD38 increases CXCL12-mediated signals and homing of chronic lymphocytic leukemia cells

CD38 increases CXCL12-mediated signals and homing of chronic lymphocytic leukemia cells

CD38 is a signaling molecule in B-cell chronic lymphocytic leukemia cells

Evolution and Function of the ADP Ribosyl Cyclase/CD38 Gene Family in Physiology and Pathology

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