Dengue Virus Serotype 1 Non-Structural Protein NS5 Expression Interferes with HIV Replication in a CD4+ T-Cell Line

Abstract

The NS5 protein expression of certain flaviviruses, such as Dengue virus type 2, West Nile virus, Hepatitis C virus, and GB virus type C, is associated with a reduced in vitro human immunodeficiency virus (HIV) viral load. To evaluate the suppression effect of the dengue virus serotype 1 (DENV1) NS5 protein on HIV replication, a CD4+ T-cell line was transfected with a plasmid that contained the coding sequence of the DENV1 NS5 gene, and later, it was infected with HIV. DENV1 NS5 protein expression suppressed HIV replication by 28.88% (P 0.005) on the fifth day compared with the control cells. These results confirm the suppression effect on HIV replication when the DENV1 NS5 protein is expressed in CD4+ T cells. Additional studies are needed to understand exactly how the DENV1 NS5 protein participates in the inhibition of HIV in vitro.HIV interaction with other infectious agents, especially in tropical regions, is associated with accelerated HIV/acquired immunodeficiency syndrome (AIDS) disease progression. However, Watt and others 1 reported that HIV and dengue interaction was associated with a reduced HIV viral load. In regard to this finding, there are only four reports on HIV and DENV interaction in humans. The first study refers to an HIV patient infected with DENV1, in which a reduction in the viral load was observed during the coinfection.1 The second study describes an HIV patient with dengue hemorrhagic fever in Brazil, 2 and the third report is a case series that includes five HIV patients infected with dengue in Singapore.3 Finally, a DENV3 and HIV coinfection in Cuba was described. 4 Previous in vitro studies have reported that NS5 protein expression in certain flaviviruses, including DENV2, West Nile virus, Hepatitis C virus, Yellow Fever virus, and GB virus type C(GBV-C), is associated with HIV replication suppression in CD4+ T cells, which is attributed to an increase in the stromal cell-derived factor-1 (SDF-1) cytokine level expression.5 SDF-1 is the principle ligand for the CXCR4 coreceptor, and it blocks HIV fusion and entry into the CD4+ T lymphocytes.6 Despite the fact that these studies have suggested that the NS5 protein expression of DENV2 and other flaviviruses is associated with elevated levels of SDF-1 expression, the participation of the NS5 polyprotein during HIV suppression is not clear. The present study evaluated the effect of DENV1 NS5 protein expression on HIV replication in a CD4+ T-cell line.An in vitro study was carried out, in which Jurkat CD4+ T-cell cultures were infected with HIV. A DENV1 NS5 gene coding sequence was introduced into the experimental group, whereas the control group was only infected with HIV. HIV p24 antigen levels were measured as a viral replication estimator at the end of the experiment. PLASMID DESIGNA pInternal Ribosome Entry Site -Enhanced Green Fluorescent Protein (pIRES-EGFP) 5.3-kb expression plasmid (Clontech) was used to introduce the coding sequence of the DENV1 NS5 gene (FJ850113; GenBank) that was synthesized by Epoch Life Science, Inc. Gene ...

Dengue Infection in a Human Immunodeficiency Virus-1 Positive Patient Chronically Infected with Hepatitis B Virus in Western Mexico

“…Watt and others 8 have reported a reduction in the HIV-1 viral load in an HIV-1-positive patient without HAART treatment who presented with dengue infection in Thailand, and demonstrated that HIV-1 replication was suppressed during the acute phase of the infection. The antiviral mechanism involved has not been described, but previous reports [23][24][25] have shown that DENV-1 and DENV-2 NS5 protein expression inhibits HIV-1 replication in Jurkat CD4 + T cells. This antiviral effect has been associated with an increase in stromal cell-derived factor 1 (SDF-1) cytokine expression and a decrease in CD4 and CXCR4 expression.…”

“…This antiviral effect has been associated with an increase in stromal cell-derived factor 1 (SDF-1) cytokine expression and a decrease in CD4 and CXCR4 expression. 24,25 SDF-1 is the principal ligand for the co-receptor CXCR4 and blocks HIV fusion and entry into the CD4 + T cell. 26 The fact that DENV NS5 protein expression could induce signaling pathway activation through the cell membrane should not be ruled out.…”

Use of Flaviviral genetic fragments as a potential prevention strategy for HIV-1 Silencing

“…For example, Gonzalez et al [36] have reported that coinfection with DV in HIV-1 infected patients resulted in stable CD4+ T cell counts and no acceleration in progression to HIV-1 to AIDS. López-Lemus et al [9] and McLinden et al [10] have shown DV NS5 expression interference with HIV-1 replication in vitro.…”

“…These mechanisms include CD4+ receptor modulations by NS4B, NS3 or NS5 proteins [8,10]. In order to determine whether HIV inhibition induced by flavivirus NS5 protein expression is conserved among additional members of the Flaviviridae, Xiang et al [12] characterized the effect of NS5 protein expression for five members of the virus family in CD4 + T cells by plasmids containing the genetic sequences of NS5 DNAs.…”

“…For example, HCV may cause hepatic failure and is the major cause of hepatocellular carcinoma in infected individuals. While most studies have reported the beneficial effects of GBV-C in HIV-1 co-infected patients, data are accumulating to show varying degrees of benefit for other flaviviruses [8][9][10][11][12]. GBV-C is a close relative of GB virus A, GB virus B, and HCV.…”