Characterization of herpes B virus isolated from wild cynomolgus macaques and its pathogenic effects in captive hosts

Despite the high seroprevalence of herpes B virus (BV) among wild macaques, it remains unclear why BV is rarely transmitted to humans who live alongside macaques in their natural habitats. We investigated disease progression, host immune responses, viral shedding, histopathology, and immunohistochemistry of tissues after BV injection in cynomolgus macaques. BV was isolated from a wild Thai cynomolgus macaque living in southern Thailand and intramuscularly injected into four captive macaques (two males and two females) housed at the Animal Biosafety Level 3 facility. Over 49 days, all macaques remained clinically healthy but showed enlarged lymph nodes. IgM was detected on 9 days post-infection (dpi) and peaked at 13 dpi, while IgG appeared on 11 dpi and peaked at 28 dpi. No viral DNA was detected in oral, urogenital, or rectal swabs throughout the 49 day study period. However, viral DNA was identified in the spleen, sublingual gland, and trigeminal ganglia. Histopathology revealed tissue damage in the spleen and trigeminal ganglion, with BV immunoreactivity in the spleen. Overall, BV injection induces localized lymphoid and immune responses without causing clinical symptoms or viral shedding in natural macaque hosts. This may help explain why natural macaque hosts remain healthy and why human BV infections associated with wild cynomolgus macaques have rarely been documented.IMPORTANCEHerpes B virus (BV) isolated from a wild cynomolgus macaque was inoculated into captive macaques in an experimental setting. BV infection triggers localized lymphoid and immune responses (IgM and IgG) without causing clinical symptoms or viral shedding. Viral DNA was detected in the spleen, sublingual gland, and trigeminal ganglia. These insights improve our understanding of how BV interacts with its natural macaque hosts and shed light on the rare transmission of BV from wild macaques to humans.