Marked immunosuppressive effects of the HIV-2 envelope protein in spite of the lower HIV-2 pathogenicity.
OBJECTIVE
HIV-1 envelope proteins have immunosuppressive properties and it is thought that they have a role in the establishment of immunodeficiency. This study characterizes the immunological effects of HIV-2 envelope protein gp105, a virus which is associated with a slower rate of disease progression.


METHODS
The effects of recombinant baculovirus-expressed envelope proteins from HIV-IIIB HIV-1MN, HIV-2ROD and SIVmac251 on anti-CD3-stimulated peripheral blood mononuclear cells (PBMC) from healthy donors were evaluated by incorporation of 3H-thymidine, flow cytometric analysis of bromodeoxyuridine incorporation in different T cell subsets, kinetics of expression of costimulatory molecules (CD40L/OX40) and assessment of cell death by annexin V/propidium iodide staining. The effects on production of tumour necrosis factor alpha (TNF-alpha) by monocytes were assessed at the single-cell level after a 6 h culture of unstimulated PBMC.


RESULTS
HIV-2 gp105 was more inhibitory than HIV-1 gp120 of T cell proliferation and the upregulation of CD40L and OX40; in the absence of signficant induction of apoptosis. This inhibition affected both CD4 and CD8 T cells and was only partially reversed by costimulation with interleukin 2 or CD28. gp105 strongly inducted TNF-alpha production by monocytes.


CONCLUSIONS
The immunosuppressive properties of the HIV envelope proteins could be beneficial rather than detrimental to the host by interfering with the heightened state of immunocellular activation that characterizes HIV infection and by limiting the bursts of viral replication. This hypothesis could in part explain the slower decline of CD4 cell numbers in HIV-2 infection and deserves further exploration.
Cavaleiro
R
R
Cellular Immunology Unit-CEBIP, Faculty of Medicine of Lisbon, University Hospital of Santa Maria, Portugal.
Sousa
A E
AE
Loureiro
A
A
Victorino
R M
RM
D017209:Apoptosis; D018106:CD28 Antigens / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology; D023201:CD40 Ligand / Q000096:biosynthesis / Q000378:metabolism; D018414:CD8-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology; D002455:Cell Division; D002478:Cells, Cultured; D004247:DNA / Q000096:biosynthesis; D005434:Flow Cytometry; D015686:Gene Products, env / Q000276:immunology*; D015488:HIV Antigens / Q000276:immunology*; D015699:HIV Envelope Protein gp120 / Q000276:immunology; D015497:HIV-1 / Q000276:immunology; D015498:HIV-2 / Q000276:immunology* / Q000472:pathogenicity; D006801:Humans; D007165:Immunosuppression Therapy; D007376:Interleukin-2 / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology; D009000:Monocytes / Q000378:metabolism; D053262:Receptors, OX40; D018124:Receptors, Tumor Necrosis Factor; D015302:Simian Immunodeficiency Virus / Q000276:immunology; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology*; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7 / Q000096:biosynthesis / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis; D054299:env Gene Products, Human Immunodeficiency Virus
D018106:CD28 Antigens; D015686:Gene Products, env; D015488:HIV Antigens; D015699:HIV Envelope Protein gp120; D007376:Interleukin-2; D053262:Receptors, OX40; D018124:Receptors, Tumor Necrosis Factor; C505716:TNFRSF4 protein, human; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7; D014409:Tumor Necrosis Factor-alpha; D054299:env Gene Products, Human Immunodeficiency Virus; C069790:gp105 envelope protein, Human immunodeficiency virus 2; D023201:CD40 Ligand; D004247:DNA