Molecular interactions between hepatitis B virus and delta virus

Abstract

HBV HBsAgs. While HBsAg 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 HBsAg 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 HBsAg 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. Core tip: Hepatitis D virus (HDV) causes accelerated liver disease in form of fulminant or chronic hepatitis in patients with hepatitis B virus (HBV) infection. HBV supports HDV replication by sharing its surface proteins. Even without overt HBV-DNA replication, transcription of HBV surface proteins (HBsAgs) remains stable in HDV infected cells, which is essential for assembly of HDV virions containing HBsAg proteins. HDV replication is oftentimes associated with a suppression of HBV-DNA levels, and several mechanisms have been suggested how HBV or HDV may influence each other's replication. Understanding molecular interactions between HBV and HDV may help to design novel therapeutic strategies. Molecular interactions between hepatitis B virus and delta virus AbstractAs 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 (HBsAgs) are present on HDV virions. The envelopment process of HDV occurs through interactions between the HDV ribonucleoprotein (RNP) complex and 36 EDITORIALSubmit a

Hepatitis delta virus facilitates the selection of hepatitis B virus mutants in vivo and functionally impacts on their replicative capacity in vitro

“…Hepatitis delta virus (HDV) co-infection or superinfection in hepatitis B virus (HBV)-infected individuals is the most severe form of chronic hepatitis. Although HBV DNA is often suppressed in co-infected patients, fluctuating or persistently high levels of HBV viraemia occur in delta hepatitis [1,2]. We recently reported the distinct mutational pattern in the HDV genome from a nationwide Iranian cohort, where the prevalence of HDV is high [3].…”

Dynamics of in vivo hepatitis D virus infection

“…As the precise impact of IFN-therapy on HDV replication is unknown, it is also possible that HDV might interfere with IFN-therapy which is acting as an eliminator of its helper virus (Shirvani- Dastgerdi and Tacke, 2015). For IFN-therapy that does not achieve this very high efficacy, we found that HBV viremia settles to a level of HBV viremia that does not represent full elimination (Fig.…”

“…The need for such high efficacy inhibition could be attributed to the omission from our model of other mechanisms such as cytolytic killing of infected cells and the loss of intracellular quantities during cell proliferation that contribute to HBV clearance (Murray and Goyal, 2015). HDV infection dramatically reduces HBV viral load while maintaining HBsAg levels (Shirvani- Dastgerdi and Tacke, 2015). Thus elimination of HDV infection might first require substantial reduction in levels of cccDNA, the HBV template, which can only be achieved by IFNtherapy with very high efficacy.…”

“…In practice though, HDV has the potential to replicate at full intensity despite low HBV viremia. This happens because HDV can actively replicate even when cccDNA only maintains its HBsAg levels (Shirvani- Dastgerdi and Tacke, 2015), which might explain some occurrences of rebound in HBV/HDV infected patients.…”

Hepatocarcinogenesis associated with hepatitis B, delta and C viruses

“…The small HDV circular genome is only ca 1.7 kb in length and is stabilized by extensive intramolecular base pairing. HDV encodes a single ORF that encodes the delta antigen (HDAg), which exists as two isoforms, the small and large HDAg [22]. HDV is considered a subviral satellite as it requires the HBV envelope proteins to form infectious virions.…”