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Host functions used by hepatitis B virus to complete its life cycle: Implications for developing host-targeting agents to treat chronic hepatitis B.

ABSTRACT: Similar to other mammalian viruses, the life cycle of hepatitis B virus (HBV) is heavily dependent upon and regulated by cellular (host) functions. These cellular functions can be generally placed in to two categories: (a) intrinsic host restriction factors and innate defenses, which must be evaded or repressed by the virus; and (b) gene products that provide functions necessary for the virus to complete its life cycle. Some of these functions may apply to all viruses, but some may be specific to HBV. In certain cases, the virus may depend upon the host function much more than does the host itself. Knowing which host functions regulate the different steps of a virus' life cycle, can lead to new antiviral targets and help in developing novel treatment strategies, in addition to improving a fundamental understanding of viral pathogenesis. Therefore, in this review we will discuss known host factors which influence key steps of HBV life cycle, and further elucidate therapeutic interventions targeting host-HBV interactions.

SUBMITTER: Mitra B

PROVIDER: S-EPMC6193490 | biostudies-other | 2018 Oct

REPOSITORIES: biostudies-other

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Host functions used by hepatitis B virus to complete its life cycle: Implications for developing host-targeting agents to treat chronic hepatitis B.

Mitra Bidisha B Thapa Roshan J RJ Guo Haitao H Block Timothy M TM

Antiviral research 20180824

Similar to other mammalian viruses, the life cycle of hepatitis B virus (HBV) is heavily dependent upon and regulated by cellular (host) functions. These cellular functions can be generally placed in to two categories: (a) intrinsic host restriction factors and innate defenses, which must be evaded or repressed by the virus; and (b) gene products that provide functions necessary for the virus to complete its life cycle. Some of these functions may apply to all viruses, but some may be specific t ...[more]

PMID: 30145242

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Project description:The development of two distinct classes of hepatitis C antiviral agents, direct-acting antivirals (DAAs) and host-targeting antivirals (HTAs), have distinctly impacted the hepatitis C virus (HCV) field by generating higher sustained virological response (SVR) rates within infected patients, via reductions in both adverse side effects and duration of treatment when compared to the old standard of care. Today DAAs are actively incorporated into the standard of care and continue to receive the most advanced clinical trial analysis. With a multitude of innovative and potent second-generation DAA compounds currently being tested in clinical trials, it is clear that the future of DAAs looks very bright. In comparison to the other class of compounds, HTAs have been slightly less impactful, despite the fact that primary treatment regimens for HCV began with the use of an HTA - interferon alpha (IFN?). The compound was advantageous in that it provided a broad-reaching antiviral response; however deleterious side effects and viral/patient resistance has since made the compound outdated. HTA research has since moved onward to target a number of cellular host factors that are required for HCV viral entry and replication such as scavenger receptor-BI (SR-BI), 3-hydroxy-3-methyl-glutaryl-CoA reductase (HMGCoA reductase), cyclophilin A (CypA), fatty acid synthase (FASN) and miRNA-122. The rationale behind pursuing these HTAs is based upon the extremely low mutational rate that occurs within eukaryotic cells, thereby creating a high genetic barrier to drug resistance for anti-HCV compounds, as well as pan-genotypic coverage to all HCV genotypes and serotypes. As the end appears near for HCV, it becomes important to ask if the development of novel HTAs should also be analyzed in combination with other DAAs, in order to address potential hard-to-treat HCV patient populations. Since the treatment regimens for HCV began with the use of a global HTA, could one end the field as well?

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Dataset Information

Host functions used by hepatitis B virus to complete its life cycle: Implications for developing host-targeting agents to treat chronic hepatitis B.

Publications

Host functions used by hepatitis B virus to complete its life cycle: Implications for developing host-targeting agents to treat chronic hepatitis B.

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