The research group, led by Chinese researcher Qinxue Hu has made progress on mechanism of herpes simplex virus type 2 (HSV-2) muclsal infection and vaccine design. Two related papers have recently been published in The Journal of Immunology.

HSV-2 is the major cause of genital herpes, and its infection increases the risk of HIV-1 acquisition and transmission. After initial infection, HSV-2 can establish latency within the nervous system and thus maintains lifelong infection in humans. It has been suggested that HSV-2 can inhibit type I IFN signaling, but the underlying mechanism has yet to be determined. In one study, they demonstrate that productive HSV-2 infection suppresses Sendai virus (SeV) or polyinosinic-polycytidylic acid-induced IFN-β production. They further reveal that US1, an immediate-early protein of HSV-2, contributes to such suppression, showing that US1 inhibits IFN-β production at both mRNA and protein levels. The findings highlight the significance of HSV-2 US1 in inhibiting IFN-β production and provide insights into the molecular mechanism by which HSV-2 evades the host innate immunity, representing an unconventional strategy exploited by a dsDNA virus to interrupt type I IFN signaling pathway.

There is a lack of an HSV-2 vaccine, in part as the result of various factors that limit robust and long-term memory immune responses at the mucosal portals of viral entry. Based on their previous findings, the research group hypothesized that using CCL19 in a fusion form to direct an immunogen to responsive immunocytes might have an advantage over CCL19 being used in combination with an immunogen. They designed two fusion constructs by fusing CCL19 to the C- or N-terminal end of the extracellular HSV-2 glycoprotein B (gB) with a linker containing two (Gly4Ser)2 repeats and a GCN4-based isoleucine zipper motif for self-oligomerization. Their findings indicate that enhanced humoral and cellular immune responses can be achieved by immunization with the gB-CCL19 fusion constructs. They further demonstrate that mice vaccinated with fusion constructs can be well protected from intravaginal lethal challenge with HSV-2, providing information for the design of vaccines against mucosal infection by HSV-2 and other sexually transmitted viruses.