The long noncoding RNA MAPKAPK5-AS1 promotes the formation of hepatitis B virus cccDNA by modulating the expression of NABP1.

Cellular long noncoding RNAs (lncRNAs) have been shown to participate in diverse biological pathways, including the regulation of virus infections. However, their functions in the hepatitis B virus (HBV) life cycle still need to be explored. Here, we conducted a loss-of-function screen targeting 1779 human lncRNAs and identified 19 lncRNAs associated with HBV infection. One lncRNA, named MAPKAPK5-AS1 (lnc-MAAS), was identified as a host factor required for HBV infection. Our data suggest that lnc-MAAS is involved in the conversion of HBV relaxed circular DNA into covalently closed circular DNA (cccDNA). Furthermore, mechanistic experiments revealed that lnc-MAAS affects cccDNA formation by modulating the expression of nucleic acid binding protein 1 (NABP1). Together, our findings shed light on the roles of host lnc-MAAS and NABP1 in HBV cccDNA formation, which may contribute to the development of novel anti-HBV therapeutics.