A research agenda for curing chronic hepatitis B virus infection

Alter, Harvey J.; Block, Timothy M.; Brown, Nathaniel; Brownstein, Alan P.; Brosgart, Carol; Chang, Kyong Mi; Chen, Pei‐Jer; Chisari, Francis V.; Cohen, Chari; El–Serag, Hashem B.; Feld, Jordan J.; Gish, Robert G.; Glenn, Jeffrey S.; Greten, Tim F.; Guo, Haitao; Guo, Ju Tao; Hoshida, Yujin; Hu, Jianming; Kowdley, Kris V.; Li, Wenhui; Liang, Jake; Locarnini, S.; Lok, Anna S.; Mason, William S.; McMahon, Brian J.; Mehta, Anand; Perrillo, Robert P.; Revill, Peter; Rice, Charles M.; Rinaudo, Jo Ann; Schinazi, Raymond F.; Seeger, Christoph; Shetty, K. Mahabala; Tavis, John E.; Zoulim, Fabien

doi:10.1002/hep.29509

Cited by 76 publications

(68 citation statements)

References 9 publications

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“…WHO is in the process of establishing a reporting system to monitor the cascade of care globally to allow for regular reporting. The potential future availability of a functional cure for HBV infection will further improve the prospects of achieving the 2030 elimination targets ( 10 ). …”

Section: Discussionmentioning

confidence: 99%

Access to Treatment for Hepatitis B Virus Infection — Worldwide, 2016

Hutin¹,

Nasrullah²,

Easterbrook³

et al. 2018

MMWR Morb. Mortal. Wkly. Rep.

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Section: Discussionmentioning

confidence: 99%

Access to Treatment for Hepatitis B Virus Infection — Worldwide, 2016

Hutin¹,

Nasrullah²,

Easterbrook³

et al. 2018

MMWR Morb. Mortal. Wkly. Rep.

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“…It is stable, and is responsible for long term viral persistence, even after years of Pol inhibitor therapy and suppression of all detectable viral DNA in the circulation (Alweiss and Dandri, 2017). Thus, targeting cccDNA is considered the most important goal in the field of anti-HBV drug design (Alter et al, 2018). The host functions involved in cccDNA formation and the drugs that target them are shown in Fig.…”

Section: Deproteination Of Viral Dna and Synthesis Of Cccdnamentioning

confidence: 99%

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

et al. 2018

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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.

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“…Approximately, 257 million people are affected due to chronic HBV infection and about 887 000 death occurs annually due to HBV infection. 1,2 The HBV was discovered by Blumberg et al 3,4 in mid-1960 when they first identified infectious agents in the blood of patients with leukaemia of Australian aborigine and called them Australia antigens. Initially it was determined to exist in the forms of rods and spheres of 22 nm.…”

Section: Introductionmentioning

confidence: 99%

Impact of length of replication competent genome of hepatitis B virus over the differential antigenic secretion

Amir

Siddiqui

Farooqui

et al. 2019

J of Cellular Biochemistry

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Hepatitis B virus (HBV) genome consists of circular partially double stranded DNA of 3.2 kb size which gets converted into covalently closed circular DNA (cccDNA) during its life cycle. It then acts as a template for formation of pregenomicRNA (pgRNA) of 3.5 kb. Absence of appropriate animal models prompted a need to establish a better in vitro culture system to uncover the propagation and survival mechanisms of the virus. There is scarcity of data to represent the significance of varying length of replication competent viral genome on the secretion of viral secretory proteins/antigens and in turn on the overall effects on the accomplishment of the viral life cycle. The present study was undertaken to ascertain a suitable replication competent construct in which the viral life cycle of HBV with varying clinical relevance can be studied efficiently. Two constructs (pHBV 1.3 and pHBV 1X) of different sizes were used to transfect hepatoma cells and consequently the secretory antigens were monitored. In vector free approach (pHBV 1X), 3.2 kb viral DNA is directly transfected in the culture system whereas in vector mediated approach more than full length of viral genome is cloned in a vector (pHBV 1.3X) and transfected to obtain a 3.5 kb pgRNA intermediate. HBV secretes two important antigens; HBsAg and HBeAg. HBsAg is a hallmark of infection and is the first to be secreted in the blood stream whereas HBeAg is a secretory protein and remains associated with the viral replication. The construct pHBV 1.3X referring to as more than full length, by virtue of being capable of undergoing transcription without the synthesis of cccDNA intermediate (unlike the clinical situation where an intermediate step of cccDNA synthesis is an essential component to initiate the viral life cycle) appears to be better system for studying viral life cycle in in vitro culture system. The reasons could be assigned to the fact that as low as 100 ng of viral DNA was shown to quantify the replicative phenotypes with this construct. The better efficiency of this construct at prima facie, appears to be mediated through the significantly higher levels of pgRNA transcript during the viral life cycle.

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A research agenda for curing chronic hepatitis B virus infection

Cited by 76 publications

References 9 publications

Access to Treatment for Hepatitis B Virus Infection — Worldwide, 2016

Access to Treatment for Hepatitis B Virus Infection — Worldwide, 2016

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

Impact of length of replication competent genome of hepatitis B virus over the differential antigenic secretion

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