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Direct-acting Antivirals and Host-targeting Agents against the Hepatitis A Virus.

Kanda T, Nakamoto S, Wu S, Nakamura M, Jiang X, Haga Y, Sasaki R, Yokosuka O - J Clin Transl Hepatol (2015)

Bottom Line: There are two forms of antiviral agents against HAV: direct-acting antivirals (DAAs) and host-targeting agents (HTAs).Among the HTAs, amantadine and interferon-lambda 1 (IL-29) inhibit HAV IRES-mediated translation and HAV replication.Janus kinase (JAK) inhibitors inhibit La protein expression, HAV IRES activity, and HAV replication.

View Article: PubMed Central - PubMed

Affiliation: Department of Gastroenterology and Nephrology, Chiba University, Graduate School of Medicine, Inohana, Chuo-ku, Chiba, Japan.

ABSTRACT
Hepatitis A virus (HAV) infection is a major cause of acute hepatitis and occasionally leads to acute liver failure in both developing and developed countries. Although effective vaccines for HAV are available, the development of new antivirals against HAV may be important for the control of HAV infection in developed countries where no universal vaccination program against HAV exists, such as Japan. There are two forms of antiviral agents against HAV: direct-acting antivirals (DAAs) and host-targeting agents (HTAs). Studies using small interfering ribonucleic acid (siRNA) have suggested that the HAV internal ribosomal entry site (IRES) is an attractive target for the control of HAV replication and infection. Among the HTAs, amantadine and interferon-lambda 1 (IL-29) inhibit HAV IRES-mediated translation and HAV replication. Janus kinase (JAK) inhibitors inhibit La protein expression, HAV IRES activity, and HAV replication. Based on this review, both DAAs and HTAs may be needed to control effectively HAV infection, and their use should continue to be explored.

No MeSH data available.


Related in: MedlinePlus

The life cycle of the hepatitis A virus (HAV).HAVcr-1, HAV cellular receptor 1; IRES, internal ribosomal entry-site; UTR, untranslated region.
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f01: The life cycle of the hepatitis A virus (HAV).HAVcr-1, HAV cellular receptor 1; IRES, internal ribosomal entry-site; UTR, untranslated region.

Mentions: HAV is a member of the Hepatovirus genus of the Picornaviridae family. There are at least six genotypes of HAV, and three of them (I to III) are of human origin.16,17 HAV is a positive single-stranded, nonenveloped ribonucleic acid (RNA) virus of ∼7,500 bases in length. The HAV genome codes one open reading frame that encodes structural (viral protein (VP)4, VP2, VP3, and VP1) and nonstructural proteins (2A, 2B, 2C, 3A, 3B, 3C, and 3D) and is flanked by a 5′ untranslated region (UTR) and a 3′ UTR. The HAV genome is translated into a single polyprotein in a cap-independent manner, i.e. HAV exhibits IRES-mediated translation. Subsequently, the single HAV polyprotein is proteolytically processed by protease 3C and cellular protease(s) into several functional and mature proteins.13,18,19 HAV IRES-mediated translation and HAV RNA replication are important for HAV virion formation (Fig. 1). HAV 3D is the RNA-dependent RNA polymerase.18,19 In fact, HAV IRES and HAV 3C are attractive targets of antiviral drugs against HAV.


Direct-acting Antivirals and Host-targeting Agents against the Hepatitis A Virus.

Kanda T, Nakamoto S, Wu S, Nakamura M, Jiang X, Haga Y, Sasaki R, Yokosuka O - J Clin Transl Hepatol (2015)

The life cycle of the hepatitis A virus (HAV).HAVcr-1, HAV cellular receptor 1; IRES, internal ribosomal entry-site; UTR, untranslated region.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4663202&req=5

f01: The life cycle of the hepatitis A virus (HAV).HAVcr-1, HAV cellular receptor 1; IRES, internal ribosomal entry-site; UTR, untranslated region.
Mentions: HAV is a member of the Hepatovirus genus of the Picornaviridae family. There are at least six genotypes of HAV, and three of them (I to III) are of human origin.16,17 HAV is a positive single-stranded, nonenveloped ribonucleic acid (RNA) virus of ∼7,500 bases in length. The HAV genome codes one open reading frame that encodes structural (viral protein (VP)4, VP2, VP3, and VP1) and nonstructural proteins (2A, 2B, 2C, 3A, 3B, 3C, and 3D) and is flanked by a 5′ untranslated region (UTR) and a 3′ UTR. The HAV genome is translated into a single polyprotein in a cap-independent manner, i.e. HAV exhibits IRES-mediated translation. Subsequently, the single HAV polyprotein is proteolytically processed by protease 3C and cellular protease(s) into several functional and mature proteins.13,18,19 HAV IRES-mediated translation and HAV RNA replication are important for HAV virion formation (Fig. 1). HAV 3D is the RNA-dependent RNA polymerase.18,19 In fact, HAV IRES and HAV 3C are attractive targets of antiviral drugs against HAV.

Bottom Line: There are two forms of antiviral agents against HAV: direct-acting antivirals (DAAs) and host-targeting agents (HTAs).Among the HTAs, amantadine and interferon-lambda 1 (IL-29) inhibit HAV IRES-mediated translation and HAV replication.Janus kinase (JAK) inhibitors inhibit La protein expression, HAV IRES activity, and HAV replication.

View Article: PubMed Central - PubMed

Affiliation: Department of Gastroenterology and Nephrology, Chiba University, Graduate School of Medicine, Inohana, Chuo-ku, Chiba, Japan.

ABSTRACT
Hepatitis A virus (HAV) infection is a major cause of acute hepatitis and occasionally leads to acute liver failure in both developing and developed countries. Although effective vaccines for HAV are available, the development of new antivirals against HAV may be important for the control of HAV infection in developed countries where no universal vaccination program against HAV exists, such as Japan. There are two forms of antiviral agents against HAV: direct-acting antivirals (DAAs) and host-targeting agents (HTAs). Studies using small interfering ribonucleic acid (siRNA) have suggested that the HAV internal ribosomal entry site (IRES) is an attractive target for the control of HAV replication and infection. Among the HTAs, amantadine and interferon-lambda 1 (IL-29) inhibit HAV IRES-mediated translation and HAV replication. Janus kinase (JAK) inhibitors inhibit La protein expression, HAV IRES activity, and HAV replication. Based on this review, both DAAs and HTAs may be needed to control effectively HAV infection, and their use should continue to be explored.

No MeSH data available.


Related in: MedlinePlus