Cell Culture Systems and Drug Targets for Hepatitis A Virus Infection

Sasaki, Reina; Masuzaki, Ryota; Matsumoto, Naoki; Ogawa, Masahiro; Moriyama, Mitsuhiko

doi:10.3390/v12050533

Cited by 19 publications

(14 citation statements)

References 87 publications

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“…Similar to Vero cells, MA-104s can support HAstV replication as well [ 41 ]. These cell lines are also used for the study of enteric RNA viruses causing extraintestinal disease including HAV and HEV [ 135 , 136 , 137 ].…”

Section: In Vitro Tools To Study Human Enteric Rna Virusesmentioning

confidence: 99%

Experimental Methods to Study the Pathogenesis of Human Enteric RNA Viruses

Aggarwal

Hassan

Baldridge

2021

Viruses

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Every year, millions of children are infected with viruses that target the gastrointestinal tract, causing acute gastroenteritis and diarrheal illness. Indeed, approximately 700 million episodes of diarrhea occur in children under five annually, with RNA viruses norovirus, rotavirus, and astrovirus serving as major causative pathogens. Numerous methodological advancements in recent years, including the establishment of novel cultivation systems using enteroids as well as the development of murine and other animal models of infection, have helped provide insight into many features of viral pathogenesis. However, many aspects of enteric viral infections remain elusive, demanding further study. Here, we describe the different in vitro and in vivo tools available to explore different pathophysiological attributes of human enteric RNA viruses, highlighting their advantages and limitations depending upon the question being explored. In addition, we discuss key areas and opportunities that would benefit from further methodological progress.

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Section: In Vitro Tools To Study Human Enteric Rna Virusesmentioning

confidence: 99%

Experimental Methods to Study the Pathogenesis of Human Enteric RNA Viruses

Aggarwal

Hassan

Baldridge

2021

Viruses

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“…The human hepatoma cell lines Huh7 and PLC/PRF/5 were maintained in Dulbecco’s modified Eagle’s medium (DMEM; Sigma-Aldrich, Saint Louis, MO, USA) containing 10% fetal calf serum (FCS), 100 U/mL penicillin G and 200 μg/mL streptomycin at 37 °C in an atmosphere of 5% CO 2 [ 9 ]. As Huh7 and PLC/PRF/5 cells support HAV replication [ 9 , 33 , 41 ], we selected these cell lines for this study. HuhT7 cells, which are stably transformed derivates from Huh7, expressed the T7 RNA polymerase, and were maintained in DMEM (Sigma-Aldrich) containing 10% FCS, 100 U/mL penicillin G and 200 μg/mL streptomycin at 37 °C in an atmosphere of 5% CO 2 [ 22 ].…”

Section: Methodsmentioning

confidence: 99%

Knockdown of Mitogen-Activated Protein Kinase Kinase 3 Negatively Regulates Hepatitis A Virus Replication

Sasaki

Masuzaki

Matsumoto

et al. 2021

IJMS

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Zinc chloride is known to be effective in combatting hepatitis A virus (HAV) infection, and zinc ions seem to be especially involved in Toll-like receptor (TLR) signaling pathways. In the present study, we examined this involvement in human hepatoma cell lines using a human TLR signaling target RT-PCR array. We also observed that zinc chloride inhibited mitogen-activated protein kinase kinase 3 (MAP2K3) expression, which could downregulate HAV replication in human hepatocytes. It is possible that zinc chloride may inhibit HAV replication in association with its inhibition of MAP2K3. In that regard, this study set out to determine whether MAP2K3 could be considered a modulating factor in the development of the HAV pathogen-associated molecular pattern (PAMP) and its triggering of interferon-β production. Because MAP2K3 seems to play a role in antiviral immunity against HAV infection, it is a promising target for drug development. The inhibition of MAP2K3 may also prevent HAV patients from developing a severe hepatitis A infection.

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“…HAV infects humans through fecal–oral routes, when HAV-contaminated water and food are consumed. Among men who have sex with men (MSM), HAV is sexually transmitted [ 46 ], and HAV outbreaks have been observed [ 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 ]. It is noteworthy that acute hepatitis A among MSM is one of the male-dominant diseases, although, in general, no gender difference exists in patients with an HAV infection caused by HAV-contaminated water and food.…”

Section: Coinfection Of Hav With Hivmentioning

confidence: 99%

“…The inhibitory effects of interferon-alpha, interferon-gamma, interferon-lambda, ribavirin, amantadine, sirtinol, and AZD1480 as host-targeting drugs and HAV 3C cysteine protease inhibitors, as well as small interfering RNAs against HAV, as antivirals that directly act on HAV replication, have been reported [ 11 , 46 , 99 ]. Interferon has antiviral potential against HAV [ 100 , 101 ], but it is difficult to use interferon in patients with ACLF, as interferon generally has cytotoxicity.…”

Section: Prevention Of Hav Infection In Patients With Chronic LIVmentioning

confidence: 99%

Co-Occurrence of Hepatitis A Infection and Chronic Liver Disease

Sasaki

Masuzaki

Takahashi

et al. 2020

IJMS

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Hepatitis A virus (HAV) infection occasionally leads to a critical condition in patients with or without chronic liver diseases. Acute-on-chronic liver disease includes acute-on-chronic liver failure (ACLF) and non-ACLF. In this review, we searched the literature concerning the association between HAV infection and chronic liver diseases in PubMed. Chronic liver diseases, such as metabolic associated fatty liver disease and alcoholic liver disease, coinfection with other viruses, and host genetic factors may be associated with severe hepatitis A. It is important to understand these conditions and mechanisms. There may be no etiological correlation between liver failure and HAV infection, but there is an association between the level of chronic liver damage and the severity of acute-on-chronic liver disease. While the application of an HAV vaccination is important for preventing HAV infection, the development of antivirals against HAV may be important for preventing the development of ACLF with HAV infection as an acute insult. The latter is all the more urgent given that the lives of patients with HAV infection and a chronic liver disease of another etiology may be at immediate risk.

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Cell Culture Systems and Drug Targets for Hepatitis A Virus Infection

Cited by 19 publications

References 87 publications

Experimental Methods to Study the Pathogenesis of Human Enteric RNA Viruses

Experimental Methods to Study the Pathogenesis of Human Enteric RNA Viruses

Knockdown of Mitogen-Activated Protein Kinase Kinase 3 Negatively Regulates Hepatitis A Virus Replication

Co-Occurrence of Hepatitis A Infection and Chronic Liver Disease

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