Selective transmission of some HIV-1 subtype C variants might depend on Envelope stimulating dendritic cells to secrete IL-10

Autoři: Evelyn Ngwa Lumngwena aff001;  Bianca Abrahams aff004;  Liliwe Shuping aff005;  Claudia Cicala aff006;  James Arthos aff006;  Zenda Woodman aff004
Působiště autorů: Department of Medicine, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa aff001;  Institute of Infectious Disease and Molecular Medicine, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa aff002;  Institute for Medical Research and Medicinal Plants studies (IMPM), Ministry of Scientific Research and Innovation (MINRESI), Yaounde, Cameroon aff003;  Department of Integrative Biomedical Sciences, Faculty of Health Sciences, University of Cape Town, Cape Town, South Africa aff004;  National Institute for Communicable Diseases, National Health Laboratory Services, Johannesburg, South Africa aff005;  National Institute of Allergy and Infectious Diseases (NIAID), NIH, Bethesda, Maryland, United States of America aff006
Vyšlo v časopise: PLoS ONE 15(1)
Kategorie: Research Article
doi: 10.1371/journal.pone.0227533


Envelope (Env) phenotype(s) that provide transmitted founders (TF) with a selective advantage during HIV-1 transmission would be the ideal target for preventative therapy. We generated Env clones from four individuals infected with a single virus and one participant infected with multiple variants at transmission and compared phenotype with matched Envs from chronic infection (CI). When we determined whether pseudovirus (PSV) of the five TF and thirteen matched CI Env clones differed in their ability to 1) enter TZM-bl cells, 2) bind DC-SIGN, and 3) trans-infect CD4+ cells there was no association between time post-infection and variation in Env phenotype. However, when we compared the ability of PSV to induce monocyte-derived dendritic cells (MDDCs) to secrete Interleukin-10 (IL-10), we found that only TF Envs from single variant transmission cases induced MDDCs to secrete either higher or similar levels of IL-10 as the CI clones. Furthermore, interaction between MDDC DC-SIGN and Env was required for secretion of IL-10. When variants were grouped according to time post-infection, TF PSV induced the release of higher levels of IL-10 than their CI counterparts although this relationship varied across MDDC donors. The selection of variants during transmission is therefore likely a complex event dependent on both virus and host genetics. Our findings suggest that, potentially due to overall variation in N-glycosylation across variants, nuanced differences in binding of TF Env to DC-SIGN might trigger alternative DC immune responses (IRs) in the female genital tract (FGT) that favour HIV-1 survival and facilitate transmission.

Klíčová slova:

Cell binding – Cloning – Cytokines – Dendritic cells – Enzyme-linked immunoassays – HIV-1 – Immune response – Secretion


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