As a deficient virus due to the lack of envelope proteins, hepatitis D virus(HDV) causes chronic or fulminant "delta hepatitis" only in people with simultaneous hepatitis B virus(HBV) infection. HBV encodes ...As a deficient virus due to the lack of envelope proteins, hepatitis D virus(HDV) causes chronic or fulminant "delta hepatitis" only in people with simultaneous hepatitis B virus(HBV) infection. HBV encodes three types of surface proteins known as small(S), medium(M) and large(L) envelope proteins. All three types of HBV surface antigens(HBs Ags) are present on HDV virions. The envelopment process of HDV occurs through interactions between the HDV ribonucleoprotein(RNP) complex and HBV HBsA gs. While HBsA g is the only protein required by HDV, the exact interaction sites between the S protein and pre-mature HDV are not well defined yet. In fact, these sites are distributed along the S protein with some hot spots for the envelopment process. Moreover, in most clinically studied samples, HDV infection is associated with a dramatically reduced HBV viral load, temporarily or permanently, while HBsA g resources are available for HDV packaging. Thus, beyond interacting with HBV envelope proteins, controlling mechanisms exist by which HDV inhibits HBV-DNA replication while allowing a selective transcription of HBV proteins. Here we discuss the molecular interaction sites between HBs Ag and the HDV-RNP complex and address the proposed indirect mechanisms, which are employed by HBV and HDV to facilitate or inhibit each other's viral replication. Understanding molecular interactions between HBV and HDV may help to design novel therapeutic strategies for delta hepatitis.展开更多
基金Supported by The German Research Foundation(DFG Ta434/2-1 and SFB/TRR57)the Interdisciplinary Center for Clinical Research(IZKF)Aachen
文摘As a deficient virus due to the lack of envelope proteins, hepatitis D virus(HDV) causes chronic or fulminant "delta hepatitis" only in people with simultaneous hepatitis B virus(HBV) infection. HBV encodes three types of surface proteins known as small(S), medium(M) and large(L) envelope proteins. All three types of HBV surface antigens(HBs Ags) are present on HDV virions. The envelopment process of HDV occurs through interactions between the HDV ribonucleoprotein(RNP) complex and HBV HBsA gs. While HBsA g is the only protein required by HDV, the exact interaction sites between the S protein and pre-mature HDV are not well defined yet. In fact, these sites are distributed along the S protein with some hot spots for the envelopment process. Moreover, in most clinically studied samples, HDV infection is associated with a dramatically reduced HBV viral load, temporarily or permanently, while HBsA g resources are available for HDV packaging. Thus, beyond interacting with HBV envelope proteins, controlling mechanisms exist by which HDV inhibits HBV-DNA replication while allowing a selective transcription of HBV proteins. Here we discuss the molecular interaction sites between HBs Ag and the HDV-RNP complex and address the proposed indirect mechanisms, which are employed by HBV and HDV to facilitate or inhibit each other's viral replication. Understanding molecular interactions between HBV and HDV may help to design novel therapeutic strategies for delta hepatitis.