Profiling of cellular microRNA responses during the early stages of KSHV infection

Kaposi's sarcoma-associated herpesvirus (KSHV) causes a variety of cancers, including Kaposi's sarcoma (KS), primary effusion lymphoma (PEL), and multicentric Castleman disease (MCD). Host cellular microRNAs (miRNAs) play important post-transcriptional regulatory roles in gene expression and can greatly influence virus-host cell interactions. This study investigated cellular miRNA expression profiles operating in response to early stages of KSHV infection of human Burkitt lymphoma B cells (BJAB). We employed deep sequencing to analyze miRNA expression in KSHV-infected BJAB cells 15 min post infection (PI) and compared this to uninfected BJAB cells. A total of 32 known miRNAs and 28 novel miRNA candidates were differentially expressed in KSHV-infected compared to uninfected BJAB cells. Interestingly, miRNA expression profiles during the early stages of viral infection yielded comparable results when UV-inactivated KSHV was used. The deep sequencing results were further confirmed by performing real-time reverse transcription PCR. The target genes predicted to be regulated by both the known and novel miRNAs are mainly involved in assisting virus entry, inducing critical cell signaling, initiating transcription of immediate early genes, promoting latent infection, and modulating the host immune response. For the first time, we provide insight into the host cellular miRNA expression profiles in response to early stages of KSHV infection of human B cells. Furthermore, this study offers a valuable basis for further investigation on the roles of cellular miRNAs in the KSHV entry process.