핵심논문
Neurological manifestations of hepatitis E virus infection: An overview
Review
[키워드] Acute hepatitis E
extrahepatic manifestations
Guillain-barrè syndrome
hepatitis E virus
Neuralgic amyotrophy
neurological manifestations
[DOI] 10.3748/wjg.v27.i18.2090 PMC 바로가기 [Article Type] Review
[DOI] 10.3748/wjg.v27.i18.2090 PMC 바로가기 [Article Type] Review
Abstract
Hepatitis E virus (HEV) is an important cause of repeated waterborne outbreaks of acute hepatitis. Recently, several extrahepatic manifestations (EHMs) have been described in patients with HEV infection. Of these, neurological disorders are the most common EHM associated with HEV. The involvement of both the peripheral nervous system and central nervous system can occur together or in isolation. Patients can present with normal liver function tests, which can often be misleading for physicians. There is a paucity of data on HEV-related neurological manifestations; and these data are mostly described as case reports and case series. In this review, we analyzed data of 163 reported cases of HEV-related neurological disorders. The mechanisms of pathogenesis, clinico-demographic profile, and outcomes of the HEV-related neurological disorders are described in this article. Nerve root and plexus disorder were found to be the most commonly reported disease, followed by meningoencephalitis.Mechanisms of Hepatocellular Injury in Hepatitis A
Review
[키워드] bystander T cell activation
hepatitis A virus
IL-18BP deficiency
Liver injury
MAVS signaling
TIM-1 polymorphism
[DOI] 10.3390/v13050861 PMC 바로가기 [Article Type] Review
[DOI] 10.3390/v13050861 PMC 바로가기 [Article Type] Review
Abstract
Hepatitis A virus (HAV) infection is a common cause of acute viral hepatitis worldwide. Despite decades of research, the pathogenic mechanisms of hepatitis A remain incompletely understood. As the replication of HAV is noncytopathic in vitro, a widely accepted concept has been that virus-specific cytotoxic T cells are responsible for liver injury. However, accumulating evidence suggests that natural killer (NK) cells, NKT cells, and even non-HAV-specific CD8 + T cells contribute to liver damage during HAV infection. In addition, intrinsic death of virus-infected hepatocytes has been implicated as a cause of liver injury in a murine model of hepatitis A. Furthermore, genetic variations in host factors such as T cell immunoglobulin-1 (TIM1) and IL-18 binding protein (IL-18BP) have been linked to hepatitis A severity. This review summarizes the current knowledge of the mechanisms of hepatocellular injury in hepatitis A. Different mechanisms may be involved under different conditions and they are not necessarily mutually exclusive. A better understanding of these mechanisms would aid in diagnosis and treatment of diseases associated with HAV infection.The Foodborne Transmission of Hepatitis E Virus to Humans
Review
[키워드] Foodborne
hepatitis E virus
meat
shellfish
Transmission
zoonotic
[DOI] 10.1007/s12560-021-09461-5 PMC 바로가기 [Article Type] Review
[DOI] 10.1007/s12560-021-09461-5 PMC 바로가기 [Article Type] Review
Abstract
Globally, Hepatitis E virus (HEV) causes over 20 million cases worldwide. HEV is an emerging and endemic pathogen within economically developed countries, chiefly resulting from infections with genotype 3 (G3) HEV. G3 HEV is known to be a zoonotic pathogen, with a broad host range. The primary source of HEV within more economically developed countries is considered to be pigs, and consumption of pork products is a significant risk factor and known transmission route for the virus to humans. However, other foods have also been implicated in the transmission of HEV to humans. This review consolidates the information available regarding transmission of HEV and looks to identify gaps where further research is required to better understand how HEV is transmitted to humans through food. Supplementary Information The online version contains supplementary material available at 10.1007/s12560-021-09461-5.Endemicity change of hepatitis A infection necessitates vaccination in food handlers: An Indian perspective
Review
[키워드] Adolescent
Adult
control measures
endemicity
food handler
food safety
hepatitis A virus
India
outbreak
public health
vaccination
[DOI] 10.1080/21645515.2020.1868820 PMC 바로가기 [Article Type] Review
[DOI] 10.1080/21645515.2020.1868820 PMC 바로가기 [Article Type] Review
Abstract
In the last two decades, outbreaks due to the foodborne hepatitis A virus (HAV) have been frequently reported in India, with adolescents and adults primarily affected. In India, most food handlers are adolescents and young adults who might be exposed to unsatisfactory environmental conditions and poor water quality. This increases the risk of HAV infection and consequently compounds the risk of HAV transmission from food handlers to susceptible populations. Given the shift in hepatitis A endemicity from high to intermediate levels in India, implementing the vaccination of food handlers has become important as it can also contribute to the elimination of hepatitis A in India. This narrative review makes a case for hepatitis A immunization of food handlers in India considering the growing food industry, evolving food culture, and the substantial burden caused by hepatitis A outbreaks.Pharmacokinetics and Efficacy of a Potential Smallpox Therapeutic, Brincidofovir, in a Lethal Monkeypox Virus Animal Model
Research Article
[키워드] animal models
experimental therapeutics
Monkeypox
smallpox
Virology
[DOI] 10.1128/mSphere.00927-20 PMC 바로가기 [Article Type] Research Article
[DOI] 10.1128/mSphere.00927-20 PMC 바로가기 [Article Type] Research Article
Abstract
Smallpox, caused by Variola virus (VARV), was eradicated in 1980; however, VARV bioterrorist threats still exist, necessitating readily available therapeutics. Current preparedness activities recognize the importance of oral antivirals and recommend therapeutics with different mechanisms of action. Monkeypox virus (MPXV) is closely related to VARV, causing a highly similar clinical human disease, and can be used as a surrogate for smallpox antiviral testing. The prairie dog MPXV model has been characterized and used to study the efficacy of antipoxvirus therapeutics, including recently approved TPOXX (tecovirimat). Brincidofovir (BCV; CMX001) has shown antiviral activity against double-stranded DNA viruses, including poxviruses. To determine the exposure of BCV following oral administration to prairie dogs, a pharmacokinetics (PK) study was performed. Analysis of BCV plasma concentrations indicated variability, conceivably due to the outbred nature of the animals. To determine BCV efficacy in the MPXV prairie dog model, groups of animals were intranasally challenged with 9 × 10^{5} plaque-forming units (PFU; 90% lethal dose [LD_{90}]) of MPXV on inoculation day 0 (ID0). Animals were divided into groups based on the first day of BCV treatment relative to inoculation day (ID–1, ID0, or ID1). A trend in efficacy was noted dependent upon treatment initiation (57% on ID–1, 43% on ID0, and 29% on ID1) but was lower than demonstrated in other animal models. Analysis of the PK data indicated that BCV plasma exposure (maximum concentration [C_{max}]) and the time of the last quantifiable concentration (AUC_{last}) were lower than in other animal models administered the same doses, indicating that suboptimal BCV exposure may explain the lower protective effect on survival. IMPORTANCE Preparedness activities against highly transmissible viruses with high mortality rates have been highlighted during the ongoing coronavirus disease 2019 (COVID-19) pandemic. Smallpox, caused by variola virus (VARV) infection, is highly transmissible, with an estimated 30% mortality. Through an intensive vaccination campaign, smallpox was declared eradicated in 1980, and routine smallpox vaccination of individuals ceased. Today's current population has little/no immunity against VARV. If smallpox were to reemerge, the worldwide results would be devastating. Recent FDA approval of one smallpox antiviral (tecovirimat) was a successful step in biothreat preparedness; however, orthopoxviruses can become resistant to treatment, suggesting the need for multiple therapeutics. Our paper details the efficacy of the investigational smallpox drug brincidofovir in a monkeypox virus (MPXV) animal model. Since brincidofovir has not been tested in vivo against smallpox, studies with the related virus MPXV are critical in understanding whether it would be protective in the event of a smallpox outbreak.Measles outbreak risk assessment for transplant candidates and recipients
Article
[키워드] clinical research/ practice
Epidemiology
infection and infectious agents - viral
Infectious disease
[DOI] 10.1111/ajt.16278 PMC 바로가기 [Article Type] Article
[DOI] 10.1111/ajt.16278 PMC 바로가기 [Article Type] Article
Abstract
Solid organ transplant (SOT) candidates and recipients are at risk of significant morbidity and mortality from infection, including those circulating in the community from unexpected outbreaks. In late 2018-summer of 2019, a measles outbreak occurred in the New York City area, with a total of 649 cases reported. We developed a systematic 3-part approach to address measles risk in our adult SOT program through: (a) identification of nonimmune adults living in outbreak ZIP codes, (b) education focused on risk reduction for patients from outbreak ZIP codes, and (c) risk reduction for nonimmune patients. All waitlisted or previously transplanted patients residing in outbreak areas received a measles patient education handout. The electronic medical record of patients born in or after 1957 was reviewed for serologic evidence of measles immunity. Measles immunity testing was performed in patients without documentation of immunity. Patients who tested nonimmune were offered MMR vaccination or intravenous immunoglobulin depending on their transplant phase and risk profile. Thus, we demonstrate successful implementation of a systematic risk assessment during a large measles outbreak to identify and protect at-risk SOT patients. As vaccine hesitancy persists, our strategies may be increasingly relevant to transplant centers and those caring for immunocompromised patients.Hepatitis B Virus Cure: Targets and Future Therapies
Review
[키워드] cure
hepatitis B
target
Treatment
[DOI] 10.3390/ijms22010213 PMC 바로가기 [Article Type] Review
[DOI] 10.3390/ijms22010213 PMC 바로가기 [Article Type] Review
Abstract
Chronic hepatitis B virus (HBV) infection is a major global health problem. It can cause progressive liver fibrosis leading to cirrhosis with end-stage liver disease, and a markedly increased risk of hepatocellular carcinoma. In the last two decades, substantial progress has been made in the treatment of chronic hepatitis, B. However, HBV is often reactivated after stopping nucloes(t)ide analogues because antivirals alone do not directly target covalently closed circular DNA, which is the template for all viral RNAs. Therefore, although currently available antiviral therapies achieve suppression of HBV replication in the majority of patients, hepatitis B surface antigen (HBsAg) loss and seroconversion is rarely achieved despite long-term antiviral treatment (HBsAg loss of less than 10% in 5 years). Various clinical trials of agents that interrupt the HBV life cycle in hepatocytes have been conducted. Potential treatment strategies and new agents are emerging as HBV cure. A combination of current and new anti-HBV agents may increase the rate of HBsAg seroclearance; thus, optimized regimens must be validated. Here, we review the newly investigated therapeutic compounds and the results of preclinical and/or clinical trials.Emergence of Novel Reassortant H1N1 Avian Influenza Viruses in Korean Wild Ducks in 2018 and 2019
Article
[키워드] Avian Influenza
H1N1
isolates
mammal adaptation
Pathogenesis
[DOI] 10.3390/v13010030 PMC 바로가기 [Article Type] Article
[DOI] 10.3390/v13010030 PMC 바로가기 [Article Type] Article
Abstract
Influenza A virus subtype H1N1 has caused global pandemics like the “Spanish flu” in 1918 and the 2009 H1N1 pandemic several times. H1N1 remains in circulation and survives in multiple animal sources, including wild birds. Surveillance during the winter of 2018–2019 in Korea revealed two H1N1 isolates in samples collected from wild bird feces: KNU18-64 (A/ Greater white-fronted goose /South Korea/KNU18-64/2018(H1N1)) and WKU19-4 (A/wild bird/South Korea/WKU19-4/2019(H1N1)). Phylogenetic analysis indicated that M gene of KNU18-64(H1N1) isolate resembles that of the Alaskan avian influenza virus, whereas WKU19-4(H1N1) appears to be closer to the Mongolian virus. Molecular characterization revealed that they harbor the amino acid sequence PSIQRS↓GLF and are low-pathogenicity influenza viruses. In particular, the two isolates harbored three different mutation sites, indicating that they have different virulence characteristics. The mutations in the PB1-F2 and PA protein of WKU19-4(H1N1) indicate increasing polymerase activity. These results corroborate the kinetic growth data for WKU19-4 in MDCK cells: a dramatic increase in the viral titer after 12 h post-inoculation compared with that in the control group H1N1 (CA/04/09(pdm09)). The KNU18-64(H1N1) isolate carries mutations indicating an increase in mammal adaptation; this characterization was confirmed by the animal study in mice. The KNU18-64(H1N1) group showed the presence of viruses in the lungs at days 3 and 6 post-infection, with titers of 2.71 ± 0.16 and 3.71 ± 0.25 log10(TCID50/mL), respectively, whereas the virus was only detected in the WKU19-4(H1N1) group at day 6 post-infection, with a lower titer of 2.75 ± 0.51 log10(TCID50/mL). The present study supports the theory that there is a relationship between Korea and America with regard to reassortment to produce novel viral strains. Therefore, there is a need for increased surveillance of influenza virus circulation in free-flying and wild land-based birds in Korea, particularly with regard to Alaskan and Asian strains.Exosomes in Hepatitis B Virus Transmission and Related Immune Response
Review
[키워드] exosomal microRNA
Exosomes
Hepatitis B virus (HBV)
immunoregulation
Infection
[DOI] 10.1620/tjem.252.309 PMC 바로가기 [Article Type] Review
[DOI] 10.1620/tjem.252.309 PMC 바로가기 [Article Type] Review