Hepatitis viruses have long been one of the focal points of health on a global scale. In this paper, we will delve into the structure and classification of hepatitis viruses, the replication process, host immune response, pathological effects, as well as the disease transmission routes and global epidemiological characteristics, hoping to work together with you to understand hepatitis viruses more comprehensively and to provide stronger support for future prevention and treatment strategies.
1. Structure and classification of hepatitis viruses.
Hepatitis viruses are a group of pathogens that cause inflammation of the liver, including hepatitis B virus (HBV), hepatitis C virus (HCV), and hepatitis A virus (HAV). An in-depth knowledge of their structure and classification is essential for understanding the hepatitis diseases caused by these viruses.
Hepatitis B Virus (HBV): B virus is a hepatophilic virus that belongs to the Hepadnaviridae family. Its viral particles contain an outer membrane and a core that encapsulates the DNA.The DNA of HBV is a partially double-stranded, circular piece of DNA.The virus causes infection through blood, sexual transmission, or mother-to-child transmission.Hepatitis B virus (HBV) is a hepatitis B virus that is transmitted through the bloodstream.
Hepatitis C Virus (HCV): Hepatitis C virus belongs to the Flaviviridae family and is a single-stranded RNA virus. HCV is transmitted through the bloodstream, with a high risk of transmission, especially through sharing syringes, blood transfusions, or during organ transplants. Its high degree of variability makes it difficult to treat.
Hepatitis A virus (HAV): Hepatitis A virus is a small RNA virus belonging to the Picornaviridae family. HAV is transmitted through food or water, especially in areas with poor sanitation. Unlike HBV and HCV, HAV infections are usually self-limiting, and most patients acquire immunity upon recovery.
By gaining a deeper understanding of the structure and classification of these viruses, we can better understand their transmission routes, incubation periods, and pathogenic mechanisms, providing a scientific basis for prevention and treatment.
2. Hepatitis virus replication process
Hepatitis virus replication is a complex process that involves several key steps, from viral invasion of the host cell to the release of new viral particles.
2.1 Viral invasion
HBV: HBV enters the host cell by infecting specific receptors on the surface of hepatocytes. Once inside the cell, the outer envelope fuses at the inner membrane to release the viral core particles.
HCV: HCV enters host cells primarily through receptors on the surface of hepatocytes, including CD81. Once inside the cell, the viral core is released and initiates the process of its RNA synthesis.
HAV: HAV enters the host through the gut and infects hepatocytes. It utilizes specific receptors on the surface of hepatocytes to enter and release its RNA.
2.2 Genome Replication
HBV: The DNA of HBV enters the nucleus of the cell, where the viral DNA is transcribed into RNA.This RNA becomes the template for new viral particles. In turn, this RNA is reverse transcribed back into DNA to form new viral particles.
HCV: HCV is a positive-stranded RNA virus whose RNA is translated into proteins and used to generate a new RNA genome. These new RNAs are used to synthesize more viral proteins and RNAs.
HAV: HAV is also a positive-stranded RNA virus whose RNA is translated into proteins and used for new RNA synthesis.
2.3 Assembly and release of viral particles
HBV: New HBV core particles are assembled in the cytoplasm and then enter the cell surface where they are wrapped with a new envelope. Eventually, mature viral particles are released via the secretory pathway.
HCV: Assembly of HCV viral particles is accomplished primarily at the endoplasmic reticulum membrane and is released outside the cell via the secretory pathway.
HAV: Assembly and release of HAV occurs in the cytoplasm and is released outside the cell through rupture of the cytoplasmic membrane.
By understanding these key steps in viral replication, we can better understand the mechanisms of hepatitis virus infection and provide a basis for disease treatment and prevention.
3. Host immune response
The host immune system plays a key role in hepatitis virus infection, and it is a complex and coordinated defense mechanism that includes both innate and acquired immunity.
3.1 Innate immune response
Inflammatory response: Hepatitis virus infection triggers an inflammatory response in the host, leading to localized tissue inflammation, which is an early response of the immune system against the virus.
Macrophage activation: Macrophages are activated in innate immunity and are responsible for phagocytosis and clearance of viral particles.
Type I Interferon (IFN) Production: Upon sensing viral invasion, host cells produce IFN, an antiviral protein that inhibits viral replication.
3.2 Acquired Immune Response
Antibody production: Host B cells are activated to produce specific antibodies that recognize and neutralize viral particles, preventing them from entering the cell.
T-cell mediated clearance: CD8+ T-cells recognize and clear infected hepatocytes, preventing the virus from replicating within the cells.
IMMUNOMEMORY: The host immune system develops an immune memory for the hepatitis virus, allowing for a more rapid and effective response in the event of re-infection.
Despite the protective role of the host immune system, in some cases, hepatitis viruses may escape immune surveillance through a variety of mechanisms, leading to chronic or recurrent infections. Therefore, a deeper understanding of the mechanisms that regulate the immune response is essential for developing more effective hepatitis virus treatment and prevention strategies.
4. Pathologic changes caused by different types of hepatitis viruses
4.1 Hepatitis B virus (HBV)
Nucleus endosome formation: HBV infection can lead to the formation of characteristic nucleus endosomes within host hepatocytes, which are associated with cellular damage and viral replication.
HBV DNA Integration: Some chronically infected individuals may experience integration of HBV DNA into the host genome, increasing the risk of hepatocarcinogenesis.
4.2 Hepatitis C Virus (HCV)
Chronic Inflammation and Liver Fibrosis: Chronic inflammation caused by HCV infection is one of the major causes of liver fibrosis and cirrhosis.
Apoptosis: HCV infection can cause apoptosis in host hepatocytes, further exacerbating liver damage.
HCV-Associated Hepatocellular Carcinoma: Chronic HCV infection is one of the major causative factors of hepatocellular carcinoma.
4.3 Hepatitis A Virus (HAV)
Acute Inflammation and Repair: HAV infection usually leads to acute inflammation, but most infected people recover. After infection, the immune system clears the virus and the liver enters a repair phase.
An in-depth study of these pathological changes can help to understand what is common and unique about different types of hepatitis virus infections and provide a more tailored regimen for individualized treatment.
5. Latest Research Advances
The current treatment of hepatitis delta virus (HDV) infection consists of the use of interferons and is largely unsatisfactory. (Yurdaydin et. al., 2018) aimed to evaluate the existing data on treatment of HDV infection and to suggest treatment goals (possible "trial endpoints") that could be used across different clinical trials .
Results were compared with MAIT cells from hepatitis B virus (HBV) monoinfected patients and healthy controls. Unsupervised high-dimensional analysis of residual circulating MAIT cells in chronic HDV infection revealed the appearance of a compound phenotype of CD38 PD-1 CD28 CD127 PLZF Eomes Helios cells indicative of activation (Dias et. al., 2019) .
Hepatitis delta virus (HDV) coinfects with hepatitis B virus (HBV) causing the most severe form of viral hepatitis. (Miao et. al., 2019) aim to establish the global epidemiology, infection mode-stratified disease progression, and clinical outcome of HDV infection .
(Ahmed et. al., 2020) study comparison of virus concentration methods for the rt-qpcr-based recovery of murine hepatitis virus, a surrogate for sars-cov-2 from untreated wastewater. The methods with the worst recovery efficiency included the adsorption-extraction method with acidification (A), followed by PEG precipitation (F). The results suggest that absorption-extraction methods with minimal or without pre-treatment can provide suitably rapid, cost-effective and relatively straightforward recovery of enveloped viruses in wastewater .
(Hepcludex ), a first-in-class entry inhibitor, is being developed by MYR GmbH for the treatment of chronic hepatitis delta virus (HDV) and chronic hepatitis B virus (HBV) infections. Bulevirtide was recently approved in the European Union (EU) for the treatment of chronic HDV infection in HDV RNA positive adult patients with compensated liver disease. (Kang et. al., 2020) summarize the milestones in the development of bulevirtide leading to this first approval for chronic HDV .
Hepatitis B core-related antigen (HBcrAg) is linked to intrahepatic covalently closed circular DNA levels and has previously been suggested as response predictor in IFN-based treatment of hepatitis B virus (HBV) mono-infection. (Sandmann et. al., 2021) include 120 patients co-infected with HBV/HDV .
Since there is no comprehensive compilation about antiviral activities of quercetin and derivates, the aim of this review is providing a summary of their antiviral activities on a set of human viral infections along with mechanisms of action (Petrillo et. al., 2021). The following family of viruses are examined: Flaviviridae, Herpesviridae, Orthomyxoviridae, Coronaviridae, Hepadnaviridae, Retroviridae, Picornaviridae, Pneumoviridae, and Filoviridae .
 Cihan Yurdaydin, Zaigham Abbas, Maria Buti, et al. "Treating Chronic Hepatitis Delta: The Need For Surrogate Markers Of Treatment Efficacy", JOURNAL OF HEPATOLOGY, 2018.
 Joana Dias, Julia Hengst, Tiphaine Parrot, et al. "Chronic Hepatitis Delta Virus Infection Leads To Functional Impairment And Severe Loss Of MAIT Cells", JOURNAL OF HEPATOLOGY, 2019.
 Zhijiang Miao, Shaoshi Zhang, Xumin Ou, et al. "Estimating The Global Prevalence, Disease Progression, and Clinical Outcome of Hepatitis Delta Virus Infection", THE JOURNAL OF INFECTIOUS DISEASES, 2019.
 Warish Ahmed, Paul M Bertsch, Aaron Bivins, et al. "Comparison of Virus Concentration Methods for The RT-qPCR-based Recovery of Murine Hepatitis Virus, A Surrogate for SARS-CoV-2 from Untreated Wastewater", THE SCIENCE OF THE TOTAL ENVIRONMENT, 2020.
 Connie Kang, Yahiya Y Syed, "Bulevirtide: First Approval", DRUGS, 2020.
 Lisa Sandmann, Cihan Yurdaydin, Katja Deterding, et al. "HBcrAg Levels Are Associated With Virological Response to Treatment With Interferon in Patients With Hepatitis Delta", HEPATOLOGY COMMUNICATIONS, 2021.
 Amalia Di Petrillo, Germano Orrù, Antonella Fais, et al. "Quercetin and Its Derivates As Antiviral Potentials: A Comprehensive Review", PHYTOTHERAPY RESEARCH : PTR, 2021.