Exchanges in the 'a' determinant of the hepatitis B virus surface antigen revisited.

The hepatitis B virus surface antigen's (HBsAg) 'a' determinant comprises a sequence of amino acid residues located in the major hydrophilic region of the S protein, whose exchanges are closely associated with compromising the antigenicity and immunogenicity of that antigen. The HBsAg is generally present in the bloodstream of individuals with acute or chronic hepatitis B virus (HBV) infection. It is classically known as the HBV infection marker, and is therefore the first marker to be investigated in the laboratory in the clinical hypothesis of infection by this agent. One of the factors that compromises the HBsAg detection in the bloodstream by the assays adopted in serological screening in both clinical contexts is the loss of S protein antigenicity. This can occur due to mutations that emerge in the HBV genome regions that encode the S protein, especially for its immunodominant region - the 'a' determinant. These mutations can induce exchanges of amino acid residues in the S protein's primary structure, altering its tertiary structure and the antigenic conformation, which may not be recognized by anti-HBs antibodies, compromising the infection diagnosis. In addition, these exchanges can render ineffective the anti-HBs antibodies action acquired by vaccination, compromise the effectiveness of the chronically HBV infected patient's treatment, and also the HBsAg immunogenicity, by promoting its retention within the cell. In this review, the residues exchange that alter the S protein's structure is revisited, as well as the mechanisms that lead to the HBsAg antigenicity loss, and the clinical, laboratory and epidemiological consequences of this phenomenon.

Elimination of the hepatitis B virus: A goal, a challenge.

The hepatitis B elimination is a goal proposed by the WHO to be achieved by 2030 through the adoption of synergistic measures for the prevention and chronic HBV infection treatment. Complete cure is characterized by the HBV elimination from the body and is the goal of the chronic hepatitis B treatment, which once achieved, will enable the hepatitis B elimination. This, today, has been a scientific challenge. The difficulty in achieving a complete cure is due to the indefinite maintenance of a covalently closed episomal circular DNA (cccDNA) reservoir and the maintenance and persistence of an insufficient and dysfunctional immune response in chronically infected patients. Among the measures adopted to eliminate hepatitis B, two have the potential to directly interfere with the virus cycle, but with limited effect on HBV control. These are conventional vaccines-blocking transmission and antiviral therapy-inhibiting replication. Vaccines, despite their effectiveness in protecting against horizontal transmission and preventing mother-to-child vertical transmission, have no effect on chronic infection or potential to eliminate the virus. Treatment with antivirals suppresses viral replication, but has no curative effect, as it has no action against cccDNA. Therapeutic vaccines comprise an additional approach in the chronic infection treatment, however, they have only a modest effect on the immune system, enhancing it temporarily. This manuscript aims to address (1) the cccDNA persistence in the hepatocyte nucleus and the immune response dysfunction in chronically infected individuals as two primary factors that have hampered the treatment and HBV elimination from the human body; (2) the limitations of antiviral therapy and therapeutic vaccines, as strategies to control hepatitis B; and (3) the possibly promising therapeutic approaches for the complete cure and elimination of hepatitis B.

Physicochemical effects of emerging exchanges on the spike protein's RBM of the SARS-CoV-2 Omicron subvariants BA.1-BA.5 and its influence on the biological properties and attributes developed by these subvariants.

Emerging in South Africa, SARS-CoV-2 Omicron variant was marked by the expression of an exaggerated number of mutations throughout its genome and by the emergence of subvariants, whose attributes developed by them have been associated with amino acid exchanges that occur mainly in the RBM region of the spike protein. The RBM comprises a region within the RBD and is directly involved in the SARS-CoV-2 spike protein interaction with the host cell ACE2 receptor, during the infection mechanism and viral transmission. Defined as the region from aa 437 to aa 508, there are several residues in certain positions that interact directly with the human ACE-2 receptor during these processes. The occurrence of amino acid exchanges in these positions causes physicochemical alterations in the SARS-CoV-2 spike protein, which confer additional advantages and attributes to the agent. In addition, these exchanges serve as a basis for the characterization of new variants and subvariants of SARS-CoV-2. In this review, the amino acid exchanges that have occurred in the RBM of the subvariants BA.1 to BA.5 of SARS-CoV-2 that emerged from the Omicron are described. The physicochemical effects caused by them on spike protein are also described, as well as their influence on the biological properties and attributes developed by the subvariants BA.1, BA.2, BA.3, BA.4 and BA.5.

Unusual serological profile in hepatitis B virus (HBV) infection associated with a probable clinical case of acute exacerbation of pre-existing chronic HBV infection.

BACKGROUND: Acute or chronic HBV infection in an individual can be laboratory characterized according to the serological profile of the viral markers in the bloodstream, and the dynamics monitoring of these markers is necessary to assess the disorder course and the infection outcome. However, under certain circumstances unusual or atypical serological profiles may be observed in both acute and chronic HBV infection. They are considered as such because they do not properly characterize the form or infection clinical phase or because they seem inconsistent, considering the viral markers dynamics in both clinical contexts. This manuscript comprises the analysis of an unusual serological profile in HBV infection. METHODS AND RESULTS: This clinical-laboratory study, had as reference a patient who presented clinical profile suggestive of acute HBV infection after recent exposure, whose laboratory data were initially compatible with this clinical presentation. However, the serological profile analysis and its monitoring demonstrated unusual pattern of viral markers expression, which has been observed in several clinical contexts, and is often associated a number of agent- or host-related factors. CONCLUSION: The serological profile analyzed here, associated with the biochemical markers serum levels found, is indicative of active chronic infection, consequence of viral reactivation. This finding suggests that in the event of unusual serological profiles in HBV infection, if the influence of agent- or host-related factors is not properly considered and neither the viral markers dynamics properly analyzed, there may be mistake in the infection clinical diagnosis, especially when the patient's clinical and epidemiological history is unknown.

Vertical transmission of hepatitis B virus from father to child: what can be concluded about this possibility?

Vertical hepatitis B virus (HBV) transmission is defined as transmission that occurs during pregnancy or postpartum from an HBV-infected mother to her fetus or child. It is an efficient route for the spread of HBV and is responsible for most of the cases of chronic HBV infection in adults. During pregnancy, vertical transmission can occur in the intrauterine phase, by placental infection via peripheral blood mononuclear cells, by placental leakage, or through female germ cells.The detection of HBV DNA in semen and spermatids from HBV-infected men has provided strong evidence that the male genital tract may act as a reservoir of the virus in HBV-infected men, supporting the possibility that vertical HBV transmission from an HBV-infected father to his child may also occur via the germ line at the time of fertilization, as occurs in HBV transmission from mother to child. Furthermore, it has been shown that integration of the HBV genome into the sperm cell genome can compromise sperm morphology and function and even cause hereditary or congenital biological effects in the offspring when an HBV-infected sperm fuses with an ovum.Since vertical HBV transmission from father to child can be a topic of interest and of global importance for controlling the spread of HBV, this article addresses the evidence supporting its occurrence via germ cells, the biological impact of integration of the HBV genome into the male germ cell genome, and the role of maternal immunoprophylaxis in vertical HBV transmission from father to child.

Clinical-laboratory profile of children and adolescents with multisystem inflammatory syndrome temporarily associated with COVID-19 in Goiás, Brazil.

Here, we describe the clinical and laboratory characteristics of patients diagnosed with multisystem inflammatory syndrome in children (MIS-C) in the state of Goiás, Brazil, and its possible association with COVID-19. The study subjects were individuals aged between 0 and 19 years, selected from private and public institutions from May 2020 to April 2022. Thirty-five cases of MIS-C were confirmed. Four progressed to death. Most of the patients were 0-9 years old. All had fever, and 71.4% had abdominal pain. All had elevated levels of inflammatory markers, and 40.0% were positive for SARS-CoV-2 by RT-PCR. This study demonstrates a broad relationship between MIS-C and SARS-CoV-2 infection. Further studies are needed to confirm this association.

Expression and detection of anti-HBs antibodies after hepatitis B virus infection or vaccination in the context of protective immunity.

Anti-HBs antibodies develop after natural infection with hepatitis B virus (HBV) or vaccination against this virus, as a result of activation of the human immune system by the HBV surface antigen (HBsAg). Anti-HBs-positive individuals are immunologically competent against HBV infection. This immunity is determined by the antibody levels in the bloodstream after resolution of natural infection or after vaccination. Anti-HBs antibody levels have been observed to decrease to below the protective level years after natural infection or vaccination, and there is reason to doubt that protective immunity to HBV is maintained after that. Factors that affect the maintenance of the anti-HBs antibody level in the bloodstream have been reported. Maintenance of immunity to HBV has been reported in anti-HBs negative individuals and those with detectable but low levels after natural infection or after vaccination. On the other hand, detection of anti-HBs antibodies without protective activity has also been observed. The presence or absence of anti-HBs antibodies in the context of HBV immunity has been the subject of extensive discussion and clinical, laboratory and epidemiological interest. These three scenarios of the anti-HBs response are discussed in this review article.

The serological markers of acute infection with hepatitis A, B, C, D, E and G viruses revisited.

Viral hepatitis is a liver infection caused by one of the six hepatitis viruses: hepatitis A, B, C, D, E, and G virus (HAV to HEV and HGV). These agents differ in their biological, immunological, pathological and epidemiological characteristics. They cause infections that, when symptomatic, lead to clinical manifestations and laboratory findings that are not specific to a particular virus, often making differential diagnosis difficult, especially when no knowledge is available regarding the patient's medical history or the epidemiological background. A number of acute-phase serological markers, such as anti-HAV, anti-HBc, anti-HDV and anti-HEV IgM antibodies, are able to provide a clear indication of an infection caused by HAV, HBV, HDV or HEV. Anti-HCV antibodies and HGV/RNA are used for the diagnosis of HCV and HGV infections. The importance of each of these markers will be reviewed, and different factors that can interfere with the diagnosis of acute infections caused by these viruses will be described.

Enzyme-linked immunosorbent/chemiluminescence assays, recombinant immunoblot assays and nucleic acid tests in the diagnosis of HCV infection.

The diagnosis of hepatitis C virus (HCV) infection is defined according to the results obtained from screening assays, and confirmation made by supplemental tests, in order to exclude the possibility of false-positive and false-negative results and, therefore, a misdiagnosis. Identifying the patient's true clinical status is of crucial importance to direct an accurate course of therapy, but, often, the definition of this status is only possible after conjunctions and analysis of the results obtained from each methodology applied, considering the limitations of each assay. In this manuscript, it is discussed briefly the possible results obtained from the three methods most commonly applied in routine laboratory and their contribution in the diagnosis of HCV infection.

Genomic detection of human immunodeficiency virus (HIV) by nucleic acid amplification test in a frequent platelet donor during the pre-seroconversion period.

Since serological donor-screening tests for HIV were introduced in 1985, the safety of donated blood components has improved dramatically. However, these tests do not completely prevent the risk of transfusion-associated HIV infection related to the use of blood donated during the pre-seroconversion window period. Testing based on nucleic acid amplification is being implemented to screen for HIV-infected blood donated during this period, which has reduced the probability of transmitting HIV through transfusion by shortening the window period. This article describes a case of acute HIV-1 infection, detected using a nucleic acid amplification test (NAT) in a repeat blood donor who donated during the pre-seroconversion window period and whose antigen and anti-HIV antibody expression was observed after molecular marker detection. In addition, the possible route of infection is discussed based on the patient's history, and finally, the need for NAT technology for blood donor screening is emphasized.

The underlying mechanisms for the "isolated positivity for the hepatitis B surface antigen (HBsAg)" serological profile.

During HBV infection, four structural antigen/antibody systems are observed: hepatitis B surface antigen (HBsAg) and its antibody (anti-HBs); the pre-S antigens associated with HBsAg particles and their antibodies; the particulate nucleocapsid antigen (HBcAg) and anti-HBc; and an antigen structurally related to HBcAg, namely HBeAg and its antibody (anti-HBe). Through the examination of this antigen-antibodies system, hepatitis B infection is diagnosed and the course of the disorder may be observed. Isolated HBsAg seropositivity is a peculiar serological pattern in HBV infection observed some times in routine laboratory. In most cases is not clear how this profile should be interpreted neither its significance. This pattern, however, may be associated with some clinical and laboratorial situations of great relevance, some of which will be addressed in this article.

Hidden hazards of HCV transmission.

Hepatitis C virus infection is a global health problem that has important epidemiological and clinical consequences. It has been well established that exposure to infected blood is the main risk factor for HCV transmission. However, in 20% of cases the agent transmission occurs by unknown route or in the presence of an unidentified source of infection. Understanding of the epidemiology of HCV is needed to help us define future control and preventive strategies. Herein, we discuss about diagnosis of HCV infection and hepatitis C surveillance in the context of its transmission.