Impact of HIV-1 infection on herpes simplex virus type 2 genetic variability among co-infected individuals

Abstract

Herpes simplex virus type 2 (HSV-2) is the most common cause of genital ulcer disease worldwide. While the contribution of HSV-2 to acquisition and course of human immunodeficiency virus (HIV) infection has been well described, less attention has been paid to the impact of HIV infection on the variability and the pathophysiology of HSV-2 infection. The goal of the present study was to characterize genotypically and phenotypically HSV-2 strains isolated from 12 patients infected by HIV-1 and from 12 HIV-negative patients. Replication capacity analyses were carried out in Vero cells and full-length nucleotide sequences were determined for glycoproteins B (gB), D (gD), G (gG), thymidine kinase (TK), and DNA polymerase (POL) HSV-2 genes. Sequence alignments and phylogenetic trees were performed. No significant differences were found in terms of replication capacity. The interstrain nucleotide identities of the 3 glycoprotein genes (gB, gC, and gG) ranged from 99.5% to 100% among the 24 HSV-2 strains. The phylogenetic analysis showed no clustering of HSV-2 strains when correlating to the HIV status of the patients. A lower variability was observed for the functional proteins TK and DNA polymerase (98.9% to 100% identity). Genetic analysis of TK evidenced mutations related to acyclovir-resistance in two HSV-2 strains. No specific differences regarding replication capacity and gene sequence were found when comparing HSV-2 strains isolated from patients infected with HIV-1 and HIV-negative patients, suggesting that the virological properties of HSV-2 infection are not influenced by HIV-1 infection among co-infected patients.

Keywords: DNA polymerase; HSV-2 genetic variation; glycoprotein B; glycoprotein C; glycoprotein G; thymidine kinase.