Acute HSV-2 infection with a low-passage clinical strain: Analysis of viral tropism, immunity, and disease manifestations in a dual animal model system.

Herpes simplex virus type 2 (HSV-2) is the primary causative agent of genital herpes and represents a substantial global health concern. Although laboratory-adapted HSV-2 strains have been widely studied, the natural virological and pathogenic features of clinical isolates remain less well understood. In this study, we characterized HSV-2/KM-1, a low-passage clinical isolate (passage 6) from China, using both guinea pig and mouse models. Intravaginal inoculation resulted in acute genital lesions, viral shedding (which peaked between 2 and 5 days post-infection (DPI), and systemic symptoms. Viral DNA was detected predominantly in the sacral dorsal root ganglia (DRG), vagina, and bladder. Guinea pigs displayed Th2-biased immune responses, marked by elevated interleukin-4 (IL-4) and interleukin-10 (IL-10), while mice mounted combined Th1 [iInterferon-gamma (IFN-γ), interleukin-2 (IL-2)] and Th2 (IL-4, IL-10) responses. Histopathological examination revealed acute inflammation in genital and bladder tissues but no neural damage in the examined neural tissues (DRG), suggesting initial viral invasion and replication prior to the establishment of full latency. Overall, the clinical relevance of HSV-2/KM-1 and its applicability in both animal models, with a 50% lethal dose (LD50) of 4.1 × 104 plaque-forming units (PFU) in guinea pigs and 4.7 × 102 PFU in mice, establish its value for pathogenesis research and therapeutic evaluation.