Experimental model to study co-infection of human immunodeficiency virus-type 1 (HIV-1IIIB) and influenza virus in cell culture

Abstract

People living with human immunodeficiency virus (HIV) demonstrate highly expressed immune deficiency and are vulnerable to exogenous viral infections (co-infections), including influenza. We were interested in developing an in vitro model to examine HIV-1 and influenza virus (Flu) co-infection based on HIV-1 sialoglycoprotein (Sgp) synthesis and virus replication in double-infected cells. A convenient and reproducible experimental model for studying the sialylation of HIV-1 glycoprotein 120 (Gp120) by direct radioactive precursors of sialic acid synthesis, [14C]N-acetylmannosamine) in cell culture was successfully introduced for investigation of co-infection. The co-infection provoked desialylation of viral Sgps, followed initially by decreased and later on, by increased HIV replication. Monoclonal antibodies (Mab) to the main Gp120 V3 neutralization epitope but not to broadly reactive Mab against Gp120 recognize and neutralize the newly exposed epitopes. A hypothesis was outlined that exogenous neuraminidase (NA) (Flu virus) changes the configuration of HIV-1 Gp120 through desialylation resulting in the exposure of a novel antigen. The proposed model could contribute to better understanding of pathogenesis of Flu co-infection in people living with HIV. In vivo, Flu co-infection most probably leads to desialylation of both HIV and the cell surface, thus facilitating the escape of HIV from immune control. The findings described here reflect the interaction between components of two viruses – NA of Flu virus and Sgps on HIV-1 surface without considering the cell surface. The hypothesis could be extended to other exogenous co-infections with agents containing NA in HIV-infected people.

Keywords

• HIV-1IIIB virus
• flu virus
• co-infection
• experimental model
• sialylation
• hypothesis