Interleukin 10 is Induced by Recombinant HIV-1 Nef Protein Involving the Calcium/calmodulin-dependent Phosphodiesterase Signal Transduction Pathway

Overview

Journal Proc Natl Acad Sci U S A

Specialty Science

Date 1997 Apr 1

PMID 9096366

Citations 25

Authors

E Brigino

S Haraguchi

A Koutsonikolis

G J Cianciolo

U Owens

R A GOOD

N K Day

Affiliations

Soon will be listed here.

Abstract

HIV-1 Nef protein shares a significant homology with the immunosuppressive and highly conserved retroviral transmembrane protein p15E. In the present study, extracellular Nef protein is shown to induce interleukin (IL)-10 mRNA expression in human peripheral blood mononuclear cells as well as in cells of H9 T and U937 promonocytic human cell lines. Release of IL-10 protein into supernatants of peripheral blood mononuclear cells stimulated with Nef is dose-dependent. Expression of cytokines IL-2, IL-4, IL-5, IL-12 p40, IL-13, and interferon gamma is not affected by Nef stimulation. IL-10 protein production induced by Nef is inhibited by the calcium/calmodulin phosphodiesterase inhibitor W-7 but not by the protein kinase A inhibitor H-89 nor the protein kinase C inhibitors staurosporine and calphostin C. The calcium chelating agent EGTA also inhibits the IL-10 production induced by Nef, and this inhibition is reversed by the addition of calcium along with Nef. These findings indicate that extracellular Nef may contribute to the immunopathogenesis of HIV infection by inducing IL-10.

Citing Articles

Examining Chronic Inflammation, Immune Metabolism, and T Cell Dysfunction in HIV Infection.

Mu W, Patankar V, Kitchen S, Zhen A Viruses. 2024; 16(2).

PMID: 38399994 PMC: 10893210. DOI: 10.3390/v16020219.

Slow Release of HIV-1 Protein Nef from Vesicle-like Structures Is Inhibited by Cytosolic Calcium Elevation in Single Human Microglia.

Stenovec M, Lasic E, Puzar Dominkus P, Trkov Bobnar S, Zorec R, Lenassi M Mol Neurobiol. 2018; 56(1):102-118.

PMID: 29679260 DOI: 10.1007/s12035-018-1072-2.

PKC-δ isoform plays a crucial role in Tat-TLR4 signalling pathway to activate NF-κB and CXCL8 production.

Serrero M, Planes R, Bahraoui E Sci Rep. 2017; 7(1):2384.

PMID: 28539656 PMC: 5443767. DOI: 10.1038/s41598-017-02468-8.

HIV-1 Tat Protein Induces Production of Proinflammatory Cytokines by Human Dendritic Cells and Monocytes/Macrophages through Engagement of TLR4-MD2-CD14 Complex and Activation of NF-κB Pathway.

Ben Haij N, Planes R, Leghmari K, Serrero M, Delobel P, Izopet J PLoS One. 2015; 10(6):e0129425.

PMID: 26090662 PMC: 4474861. DOI: 10.1371/journal.pone.0129425.

HIV-1 Myristoylated Nef Treatment of Murine Microglial Cells Activates Inducible Nitric Oxide Synthase, NO2 Production and Neurotoxic Activity.

Mangino G, Famiglietti M, Capone C, Veroni C, Percario Z, Leone S PLoS One. 2015; 10(6):e0130189.

PMID: 26066624 PMC: 4465743. DOI: 10.1371/journal.pone.0130189.

References

Saville M, Taga K, Foli A, Broder S, Tosato G, Yarchoan R . Interleukin-10 suppresses human immunodeficiency virus-1 replication in vitro in cells of the monocyte/macrophage lineage. Blood. 1994; 83(12):3591-9. View

Collette Y, Dutartre H, Benziane A, Olive D . Similarity between Nef of primate lentiviruses and p15E of murine and feline leukaemia viruses. AIDS. 1996; 10(4):441-2. DOI: 10.1097/00002030-199604000-00013. View

Chirmule N, Oyaizu N, Saxinger C, Pahwa S . Nef protein of HIV-1 has B-cell stimulatory activity. AIDS. 1994; 8(6):733-4. DOI: 10.1097/00002030-199406000-00002. View

Barcellini W, Rizzardi G, Borghi M, Fain C, Lazzarin A, Meroni P . TH1 and TH2 cytokine production by peripheral blood mononuclear cells from HIV-infected patients. AIDS. 1994; 8(6):757-62. DOI: 10.1097/00002030-199406000-00006. View

Cullen B . The role of Nef in the replication cycle of the human and simian immunodeficiency viruses. Virology. 1994; 205(1):1-6. DOI: 10.1006/viro.1994.1613. View

Akridge R, Oyafuso L, Reed S . IL-10 is induced during HIV-1 infection and is capable of decreasing viral replication in human macrophages. J Immunol. 1994; 153(12):5782-9. View

Otake K, Fujii Y, Nakaya T, Nishino Y, Zhong Q, Fujinaga K . The carboxyl-terminal region of HIV-1 Nef protein is a cell surface domain that can interact with CD4+ T cells. J Immunol. 1994; 153(12):5826-37. View

Kirchhoff F, Greenough T, Brettler D, Sullivan J, Desrosiers R . Brief report: absence of intact nef sequences in a long-term survivor with nonprogressive HIV-1 infection. N Engl J Med. 1995; 332(4):228-32. DOI: 10.1056/NEJM199501263320405. View

Kaminchik J, Margalit R, Yaish S, Drummer H, Amit B, Sarver N . Cellular distribution of HIV type 1 Nef protein: identification of domains in Nef required for association with membrane and detergent-insoluble cellular matrix. AIDS Res Hum Retroviruses. 1994; 10(8):1003-10. DOI: 10.1089/aid.1994.10.1003. View

10.

Clerici M, Shearer G . The Th1-Th2 hypothesis of HIV infection: new insights. Immunol Today. 1994; 15(12):575-81. DOI: 10.1016/0167-5699(94)90220-8. View

11.

CURTAIN C, Separovic F, Rivett D, Kirkpatrick A, Waring A, Gordon L . Fusogenic activity of amino-terminal region of HIV type 1 Nef protein. AIDS Res Hum Retroviruses. 1994; 10(10):1231-40. DOI: 10.1089/aid.1994.10.1231. View

12.

Baur A, Sawai E, Dazin P, Fantl W, Cheng-Mayer C, Peterlin B . HIV-1 Nef leads to inhibition or activation of T cells depending on its intracellular localization. Immunity. 1994; 1(5):373-84. DOI: 10.1016/1074-7613(94)90068-x. View

13.

Haraguchi S, GOOD R, Cianciolo G, Day N . Differential modulation of Th1- and Th2-related cytokine mRNA expression by a synthetic peptide homologous to a conserved domain within retroviral envelope protein. Proc Natl Acad Sci U S A. 1995; 92(8):3611-5. PMC: 42217. DOI: 10.1073/pnas.92.8.3611. View

14.

Trono D . HIV accessory proteins: leading roles for the supporting cast. Cell. 1995; 82(2):189-92. DOI: 10.1016/0092-8674(95)90306-2. View

15.

Popovic M, Gallo R . T4 positive human neoplastic cell lines susceptible to and permissive for HTLV-III. Lancet. 1984; 2(8417-8418):1472-3. DOI: 10.1016/s0140-6736(84)91666-0. View

16.

Cianciolo G, Copeland T, Oroszlan S, Snyderman R . Inhibition of lymphocyte proliferation by a synthetic peptide homologous to retroviral envelope proteins. Science. 1985; 230(4724):453-5. DOI: 10.1126/science.2996136. View

17.

Mitani M, Cianciolo G, Snyderman R, Yasuda M, GOOD R, Day N . Suppressive effect on polyclonal B-cell activation of a synthetic peptide homologous to a transmembrane component of oncogenic retroviruses. Proc Natl Acad Sci U S A. 1987; 84(1):237-40. PMC: 304178. DOI: 10.1073/pnas.84.1.237. View

18.

Frankel A, Pabo C . Cellular uptake of the tat protein from human immunodeficiency virus. Cell. 1988; 55(6):1189-93. DOI: 10.1016/0092-8674(88)90263-2. View

19.

Ameisen J, Guy B, Chamaret S, Loche M, MACH B, Tartar A . Persistent antibody response to the HIV-1-negative regulatory factor in HIV-1-infected seronegative persons. N Engl J Med. 1989; 320(4):251-2. DOI: 10.1056/NEJM198901263200415. View

20.

Bentin J, Tsoukas C, McCutchan J, Spector S, Richman D, Vaughan J . Impairment in T-lymphocyte responses during early infection with the human immunodeficiency virus. J Clin Immunol. 1989; 9(2):159-68. DOI: 10.1007/BF00916944. View