DOCK11 and DENND2A play pivotal roles in the maintenance of hepatitis B virus in host cells

Abstract

Human hepatitis B virus (HBV) infection remains a serious health problem worldwide. However, the mechanism for the maintenance of HBV in a latent state within host cells remains unclear. Here, using single-cell RNA sequencing analysis, we identified four genes linked to the maintenance of HBV in a liver cell line expressing HBV RNA at a low frequency. These genes included DOCK11 and DENND2A, which encode small GTPase regulators. In primary human hepatocytes infected with HBV, knockdown of these two genes decreased the amount of both HBV DNA and covalently closed circular DNA to below the limit of detection. Our findings reveal a role for DOCK11 and DENND2A in the maintenance of HBV.

Guanine nucleotide exchange factor DOCK11-binding peptide fused with a single chain antibody inhibits hepatitis B virus infection and replication

“…Each mechanism is required for HBV attachment and entry, transport to the nucleus, and formation of cccDNA. DOCK11 is reported to be the GEF for Rho GTPase Cdc42 ( 12) and identified as an essential host factor that mediates HBV infection (11). Although Cdc42 also affect HBV proliferation and DOCK11-Cdc42 signaling pathway is indicated to be essential in the HBV infection (11), the role of DOCK11 activity with Cdc42 has not been clarified.…”

“…HBV infection of PXB cells (primary human hepatocytes) purchased from PhoenixBio Co was performed as previously described (11). Briefly, PXB cells were cultured without passage.…”

“…DOCK11 has been identified as a host factor that is necessary for intracellular maintenance of HBV (11). DOCK family members function as guanine nucleotide exchange factors (GEFs), and DOCK11 is specific for Cdc42 (12).…”

Hepatitis B Virus Utilizes a Retrograde Trafficking Route via the Trans-Golgi Network to Avoid Lysosomal Degradation

“…We identified the host factors that were differentially up-regulated in HBV-positive HC1 cells compared with HBV-negative HC1 cells using single-cell transcriptome analysis. 2 One of the identified host factors was dedicator of cytokinesis 11 (DOCK11). 3 …”

LINC02544 modulates the RAB/RAS signaling pathway by potential regulation of DENND2A expression level in the breast cancer patients: integrated bioinformatics and experimental analyses

“…It is important to note that previous studies revealed that DENND2A could have a key role in Hepatitis B [23] and non-small cell lung cancer [24]. However, the main role of DENND2A in breast cancer remained unclear.…”