Hepatitis A: Viral Structure, Classification, Life Cycle, Clinical Symptoms, Diagnosis Error, and Vaccination

Abstract

Hepatitis A virus (HAV) is one of the well-known viruses that cause hepatitis all around the globe. Although this illness has decreased in developed countries due to extensive immunization, numerous developing and under-developed countries are struggling with this virus. HAV infection can be spread by oral-fecal contact, and there are frequent epidemics through nutrition. Improvements in socioeconomic and sanitary circumstances have caused a shift in the disease's prevalence worldwide. Younger children are usually asymptomatic, but as they become older, the infection symptoms begin to appear. Symptoms range from slight inflammation and jaundice to acute liver failure in older individuals. While an acute infection may be self-limiting, unrecognized persistent infections, and the misapplication of therapeutic methods based on clinical guidelines are linked to a higher incidence of cirrhosis, hepatocellular carcinoma, and mortality. Fortunately, most patients recover within two months of infection, though 10-15% of patients will relapse within the first six months. A virus seldom leads to persistent infection or liver damage. The mainstay of therapy is based on supportive care. All children from 12-23 months, as well as some susceptible populations, should receive routine vaccinations, according to the Centers for Disease Control and Prevention and the American Academy of Pediatrics. Laboratory diagnosis of HAV is based on antigen detection, checking liver enzyme levels, and antibody screening. Furthermore, polymerase chain reaction (PCR) technology has identified HAV in suspected nutrition sources; therefore, this technique is used for preventative measures and food-related laws.

Figure 1

P1 1A-VP4, 1B-VP2, 1C-VP3, and 1D-VP1 are structural protein components making up the capsid polypeptide. P2 comprises of three nonstructural polypeptides: 2A, 2B, and 2C, all required for viral replication. P3 consists of four nonstructural proteins: 3A anchors the replication component to the cell membranes, 3B is a protein that is also called VPg. At the same time, 3C is a cysteine protease that breaks down polypeptides into proteins, and 3D is an RNA polymerase that requires RNA to function.

Figure 2

HAV replication cycle. At the hepatocyte's basolateral membrane, the HAV virus interacts with host cell receptors, and its uncoated RNA is released into the cytoplasm. The cap-independent, IRES-driven translation of the positive-strand RNA genome produces polyproteins. Nonstructural proteins involved in genome replication (2B, 2C, 3AB, 3Dpol), the protease (3Cpro), and capsid proteins are produced by proteolytic processing of polyprotein. 2BC causes alterations in intracellular membranes, leading to the formation of a membrane-bound replicase complex that guides the production of a matching minus-strand RNA, which is subsequently employed as a template to make numerous new replicas of the RNA genome. Newly generated positive-strand RNAs are instructed to do more translation or RNA biosynthesis, or they can be packed into capsids to produce intracellular viral offspring. These freshly formed viral components are attracted to multivesicular bodies for eventual egress from infected cells into the biliary canaliculus or hepatic sinusoids via the apical plasma membrane and basolateral plasma membranes, respectively. The RNA genome is exposed after entering the cell, and the host ribosomes attach it to create polysomes. A viral RNA polymerase translation synthesizes viral particles that can be assembled and released into the biliary tree.

Figure 3

Different methods can be used to diagnose HAV infection, such as (a) specific diagnosis based on antibody detection: IgM antibodies are presented in the early stages, whereas IgG antibodies can persist for up to 6 months after infection. ELISA and immunochromatographic-based assays are used to differentiate between antibodies. Additional tests include (b) checking the level of liver enzymes and serum bilirubin and (c) molecular methods such as PCR to detect the virus genome.

Figure 4

The Centers for Disease Control and Prevention (CDC) recommend hepatitis A vaccination for different groups of populations, including one-year-old children, all children and teens up to age 18 who have not previously been vaccinated, certain children aged 6–11 months who are traveling outside of their countries, all adults who are at risk, or adults who do not have a risk factor but want to avoid hepatitis A infection.