Brugia malayi Antigen (BmA) Inhibits HIV-1 Trans-Infection but Neither BmA nor ES-62 Alter HIV-1 Infectivity of DC Induced CD4+ Th-Cells.

Emily E I M Mouser,William Harnett,Maria Yazdanbakhsh,William A Paxton,Georgios Pollakis,Esther C De Jong,Guido Poli

doi:10.1371/journal.pone.0146527

Emily E I M Mouser, William Harnett + Show 5 more

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https://doi.org/10.1371/journal.pone.0146527

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Abstract

One of the hallmarks of HIV-1 disease is the association of heightened CD4+ T-cell activation with HIV-1 replication. Parasitic helminths including filarial nematodes have evolved numerous and complex mechanisms to skew, dampen and evade human immune responses suggesting that HIV-1 infection may be modulated in co-infected individuals. Here we studied the effects of two filarial nematode products, adult worm antigen from Brugia malayi (BmA) and excretory-secretory product 62 (ES-62) from Acanthocheilonema viteae on HIV-1 infection in vitro. Neither BmA nor ES-62 influenced HIV-1 replication in CD4+ enriched T-cells, with either a CCR5- or CXCR4-using virus. BmA, but not ES-62, had the capacity to bind the C-type lectin dendritic cell-specific intercellular adhesion molecule-3-grabbing non-integrin (DC-SIGN) thereby inhibiting HIV-1 trans-infection of CD4+ enriched T-cells. As for their effect on DCs, neither BmA nor ES-62 could enhance or inhibit DC maturation as determined by CD83, CD86 and HLA-DR expression, or the production of IL-6, IL-10, IL-12 and TNF-α. As expected, due to the unaltered DC phenotype, no differences were found in CD4+ T helper (Th) cell phenotypes induced by DCs treated with either BmA or ES-62. Moreover, the HIV-1 susceptibility of the Th-cell populations induced by BmA or ES-62 exposed DCs was unaffected for both CCR5- and CXCR4-using HIV-1 viruses. In conclusion, although BmA has the potential capacity to interfere with HIV-1 transmission or initial viral dissemination through preventing the virus from interacting with DCs, no differences in the Th-cell polarizing capacity of DCs exposed to BmA or ES-62 were observed. Neither antigenic source demonstrated beneficial or detrimental effects on the HIV-1 susceptibility of CD4+ Th-cells induced by exposed DCs.

Highlights

Human immunodeficiency virus type 1 (HIV-1) is endemic in many regions of the world where individuals are infected with an array of pathogens [1]
SF162 (R5) and LAI (X4) outgrowth in CD4+ enriched T-cells exposed to 1, 2 or 4μg/ml excretory-secretory product 62 (ES-62) was unaffected (Fig 1B). This demonstrates that neither Brugia malayi (BmA) nor excretory secretory (ES)-62 has the capacity to prevent HIV-1 binding to CD4, CCR5 or CXCR4
We demonstrate that BmA, but not ES-62, can potently bind dendritic cell-specific intercellular adhesion molecule3-grabbing non-integrin (DC-SIGN) and inhibit HIV-1 trans-infection of CD4+ enriched T-cells, whilst neither antigen can block cis-infection

Summary

Introduction

Human immunodeficiency virus type 1 (HIV-1) is endemic in many regions of the world where individuals are infected with an array of pathogens [1]. Gp120 can bind several Ctype lectin receptors (CLR) on cells derived from the myeloid cell lineage. These cells can subsequently pass the virion to activated CD4+ T-lymphocytes, a process termed trans-infection [7]. In addition to gp120, DC-SIGN can bind many glycosylated structures including a large array of pathogen-derived glycoproteins as well as numerous host proteins found in bodily secretions. Binding of these glycoproteins to DC-SIGN can block its ability to capture and transfer HIV-1 [9,10,11,12]

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