KSHV co-infection regulates HPV16+ cervical cancer cells pathogenesis in vitro and in vivo.

High-risk human papillomavirus (HPV) infection is the etiological agent of cervical, oral and oropharyngeal cancers. Another oncogenic virus, Kaposi sarcoma-associated herpesvirus (KSHV) can cause several human cancers arising in those immunocompromised patients. KSHV DNA has been detected in the oral cavity and the female genital tract, although its detection rate in cervical samples is relatively low. Therefore, it remains unclear about the role of KSHV co-infection in the development of HPV-related neoplasia. We recently report that KSHV infection of HPV16+ cervical cancer cell line SiHa induces several pro-inflammatory factors production while reducing HPV16 E6 and E7 expression through the manipulation of cellular microRNA function. In the current study, we focus on determining the influence of KSHV co-infection on cervical cancer cells pathogenesis in vitro and in vivo. We found that KSHV co-infection is able to maintain SiHa and/or CaSki cells pathogenesis and tumorigenesis, although hijacking HPV oncogenic proteins expression. In mechanisms, KSHV co-infection is capable of increasing Macrophage migration inhibitory factor (MIF) and its receptor CXCR2 expression from cervical cancer cells, which may contribute to cervical cancer development. Our data indicate that KSHV co-infection may act as a potential co-factor to promote HPV-related neoplasia development.