KSHV co-infection, a new co-factor for HPV-related cervical carcinogenesis?

Abstract

High-risk human papillomavirus (HPV) infection is the etiological agent of cervical cancer and some other cancers. Kaposi sarcoma-associated herpesvirus (KSHV) represents a principal causative agent of several human cancers arising in those immunocompromised patients. In fact, KSHV DNA has been detected in the female genital tract, and this virus may share some transmission routes with HPV, although the detection rate of KSHV in cervical samples is very low and the KSHV/HPV co-infection is seldom reported. Currently, it remains unclear about the role of KSHV co-infection in the development of HPV-related neoplasias. In this article, we have summarized the recent finding from clinic and bench indicating KSHV co-infection may represent a co-factor for the development of HPV-related carcinogenesis.

Keywords: HPV; KSHV; cervical cancer; oncogenic virus.

Figure 1

Detection of oncogenic viruses transcripts in the RNA-Seq datasets of cervical cancer samples. One hundred RNA-Seq cervical cancer datasets were obtained from the TCGA cohort and raw sequencing reads were analyzed as previously described [57]. Each vertical bar represents an individual patient and the color intensity reflects the levels of viral transcripts.

Figure 2

The upregulation of MIF and its receptors by KSHV co-infection in HPV+ cervical cancer tissues. The mock or KSHV co-infected SiHa cells (approximately 5 × 10⁵ cells were mixed at a ratio of 1:1 with growth factor-depleted Matrigel) were injected subcutaneously into the right flanks of nude mice, respectively. The mice were observed and measured every 2~3 d for the presence of palpable tumors for ~40 d. Protein expression within tumor tissues from representative injected mice was measured by using immunohistochemistry staining.

Figure 3

Schematic of recent findings about the potential interaction of KSHV and HPV in cervical cancer cells.