scholarly journals Hepatitis A Virus-Specific Immunoglobulin A Mediates Infection of Hepatocytes with Hepatitis A Virus via the Asialoglycoprotein Receptor

2000 ◽  
Vol 74 (23) ◽  
pp. 10950-10957 ◽  
Author(s):  
Andreas Dotzauer ◽  
Ulrike Gebhardt ◽  
Karen Bieback ◽  
Ulrich Göttke ◽  
Anja Kracke ◽  
...  
Keyword(s):  
Gastrointestinal Tract ◽  
Neutralizing Antibodies ◽  
Hepatitis A ◽  
Hepatitis A Virus ◽  
Immunoglobulin A ◽  
Asialoglycoprotein Receptor ◽  
Primary Hepatocytes ◽  
Mouse Hepatocyte ◽  
Specific Immunoglobulin ◽  
Bile Fluid

ABSTRACT The mechanisms underlying the hepatotropism of hepatitis A virus (HAV) and the relapsing courses of HAV infections are unknown. In this report, we show for a mouse hepatocyte model that HAV-specific immunoglobulin A (IgA) mediates infection of hepatocytes with HAV via the asialoglycoprotein receptor, which binds and internalizes IgA molecules. Proof of HAV infection was obtained by detection of HAV minus-strand RNA, which is indicative for virus replication, and quantification of infectious virions. We demonstrate that human hepatocytes also ingest HAV–anti-HAV IgA complexes by the same mechanism, resulting in infection of the cells, by using the HepG2 cell line and primary hepatocytes. The relevance of this surrogate receptor mechanism in HAV pathogenesis lies in the fact that HAV, IgA, and antigen-IgA complexes use the same pathway within the organism, leading from the gastrointestinal tract to the liver via blood and back to the gastrointestinal tract via bile fluid. Therefore, HAV-specific IgA antibodies produced by gastrointestinal mucosa-associated lymphoid tissue may serve as carrier and targeting molecules, enabling and supporting HAV infection of IgA receptor-positive hepatocytes and, in the case of relapsing courses, allowing reinfection of the liver in the presence of otherwise neutralizing antibodies, resulting in exacerbation of liver disease.

scholarly journals Biliary Secretion of Quasi-Enveloped Human Hepatitis A Virus

mBio ◽  
2016 ◽  
Vol 7 (6) ◽  
Author(s):  
Asuka Hirai-Yuki ◽  
Lucinda Hensley ◽  
Jason K. Whitmire ◽  
Stanley M. Lemon
Keyword(s):  
Life Cycle ◽  
Bile Acids ◽  
Neutralizing Antibodies ◽  
Hepatitis A ◽  
Hepatitis A Virus ◽  
Acute Infection ◽  
Cell Culture Supernatant ◽  
Particle Type ◽  
Human Bile

ABSTRACTHepatitis A virus (HAV) is an unusual picornavirus that is released from cells cloaked in host-derived membranes. These quasi-enveloped virions (eHAV) are the only particle type circulating in blood during infection, whereas only nonenveloped virions are shed in feces. The reason for this is uncertain. Hepatocytes, the only cell type known to support HAV replicationin vivo, are highly polarized epithelial cells with basolateral membranes facing onto hepatic (blood) sinusoids and apical membranes abutting biliary canaliculi from which bile is secreted to the gut. To assess whether eHAV and nonenveloped virus egress from cells via vectorially distinct pathways, we studied infected polarized cultures of Caco-2 and HepG2-N6 cells. Most (>99%) progeny virions were released apically from Caco-2 cells, whereas basolateral (64%) versus apical (36%) release was more balanced with HepG2-N6 cells. Both apically and basolaterally released virions were predominantly enveloped, with no suggestion of differential vectorial release of eHAV versus naked virions. Basolateral to apical transcytosis of either particle type was minimal (<0.02%/h) in HepG2-N6 cells, arguing against this as a mechanism for differences in membrane envelopment of serum versus fecal virus. High concentrations of human bile acids converted eHAV to nonenveloped virions, whereas virus present in bile from HAV-infectedIfnar1−/−Ifngr1−/−andMavs−/−mice banded over a range of densities extending from that of eHAV to that of nonenveloped virions. We conclude that nonenveloped virions shed in feces are derived from eHAV released across the canalicular membrane and stripped of membranes by the detergent action of bile acids within the proximal biliary canaliculus.IMPORTANCEHAV is a hepatotropic, fecally/orally transmitted picornavirus that can cause severe hepatitis in humans. Recent work reveals that it has an unusual life cycle. Virus is found in cell culture supernatant fluids in two mature, infectious forms: one wrapped in membranes (quasi-enveloped) and another that is nonenveloped. Membrane-wrapped virions circulate in blood during acute infection and are resistant to neutralizing antibodies, likely facilitating HAV dissemination within the liver. On the other hand, virus shed in feces is nonenveloped and highly stable, facilitating epidemic spread and transmission to naive hosts. Factors controlling the biogenesis of these two distinct forms of the virus in infected humans are not understood. Here we characterize vectorial release of quasi-enveloped virions from polarized epithelial cell cultures and provide evidence that bile acids strip membranes from eHAV following its secretion into the biliary tract. These results enhance our understanding of the life cycle of this unusual picornavirus.

scholarly journals The seroprevalence of cytomegalovirus infection in Belgium anno 2002 and 2006: a comparative analysis with hepatitis A virus seroprevalence

2019 ◽  
Vol 147 ◽  
Author(s):  
G. S. A. Smit ◽  
S. Abrams ◽  
P. Dorny ◽  
N. Speybroeck ◽  
B. Devleesschauwer ◽  
...  
Keyword(s):  
Comparative Analysis ◽  
Cytomegalovirus Infection ◽  
Large Scale ◽  
Hepatitis A ◽  
Hepatitis A Virus ◽  
Age Group ◽  
Test Results ◽  
Cmv Infection ◽  
Cross Sectional ◽  
Specific Immunoglobulin

AbstractCytomegalovirus (CMV) infection is endemic worldwide but its seroprevalence varies widely. The goal of this study was to estimate the age-specific seroprevalence of CMV infection in Belgium based on two cross-sectional serological datasets from 2002 and 2006. The seroprevalence was estimated relying on diagnostic test results based on cut-off values pre-specified by the manufacturers of the tests as well as relying on mixture models applied to continuous pathogen-specific immunoglobulin G antibody titre concentrations. The age-specific seroprevalence of hepatitis A virus (HAV), based on three Belgian cross-sectional serological datasets from 1993, 2002 and 2006, was used as a comparator since individuals acquire lifelong immunity upon recovery, implying an increasing seroprevalence with age. The age group weighted overall CMV seroprevalence derived from the mixture model was 32% (95% confidence interval (CI) 31–34%) in 2002 and 31% (95% CI 30–32%) in 2006. We demonstrated that CMV epidemiology differs from the immunizing infection HAV. This was the first large-scale study of CMV and HAV serial datasets in Belgium, estimating seroprevalence specified by age and birth cohort.

scholarly journals Rapid detection of anti-hepatitis A virus neutralizing antibodies in a microplate enzyme immunoassay

2009 ◽  
Vol 58 (11) ◽  
pp. 1433-1436 ◽  
Author(s):  
Ali Azizi ◽  
Danylo Sirskyj ◽  
Richard Weltzin ◽  
David E. Anderson ◽  
Francisco Diaz-Mitoma
Keyword(s):  
Cell Culture ◽  
Rapid Detection ◽  
Neutralizing Antibodies ◽  
Hepatitis A ◽  
Slow Growth ◽  
Hepatitis A Virus ◽  
Rapid Methods ◽  
Enzymic Assay ◽  
Detection And Quantification

The slow growth of hepatitis A virus (HAV) in cell culture is one of the primary pitfalls in the development of sensitive and rapid methods for the detection and quantification of HAV and associated neutralizing antibodies. Currently, in vitro assays frequently require 8 days or more to detect and quantify the presence of HAV neutralizing antibodies. This study describes a rapid immunoassay that allowed the detection of anti-HAV neutralizing antibodies in only 3 days. This microplate-based enzymic assay may be applicable in virological diagnostics, in evaluating the immunogenicity of HAV vaccines and in quantifying neutralizing antibodies during the course of HAV infection.

scholarly journals Hyperenzymemia after vaccination against COVID-19: complex equation with simple variables

2021 ◽  
pp. 159-164
Author(s):  
L. Yu. Ilchenko ◽  
I. G. Fedorov ◽  
G. G. Totolyan ◽  
A. M. Karelina ◽  
G. A. Sedova ◽  
...  
Keyword(s):  
Neutralizing Antibodies ◽  
Hepatitis A ◽  
Hepatitis A Virus ◽  
Left Lung ◽  
Repeated Administration ◽  
Immunoglobulin M ◽  
Damage Development ◽  
Hepatocellular Damage ◽  
Coronavirus Infection ◽  
Relationship Of

The article presents clinical case of the jaundice development and severe hyperenzymemia in GAM-Covid-VAK (Sputnik V) vaccination against COVID-19 in a 69-year-old patient. History — systematic use of non-steroidal anti-inflammatory drugs due to persisting pain after knee arthroplasty in 2018; frequent trips for several years to another region for sanatorium treatment, the use of mineral water. The diseases caused by hepatitis viruses, drug damage and post-vaccination reaction were included in diagnostic search. The markers of hepatitis B and C infection viruses were not detected during the enzyme immunoassay and polymerase chain reaction. The indicator for determining the relationship of a drug with the liver damage development was 6 points (borderline value) and only indicated the likelihood of drug hepatotoxicity. At the same time, it is known from history that repeated administration of the drug did not cause liver dysfunctions. The diagnosis of coronavirus infection was established based on the identification of SARS-CoV-2 in the hospital with repeated laboratory testing and competing diagnosis of hepatitis A has been confirmed on the basis of hepatocellular damage and the presence of serological marker of hepatitis A virus (immunoglobulin M antibodies). The treatment was continued in the infectious hospital, where the diagnosis of co-infection was confirmed. The pneumofibrotic changes in the S5 region of the left lung were revealed according to computed tomography. The normalization of aminotransferase activity and bilirubin was noted during dynamic observation. Apparently HAV infection led to a decrease in the immune response, the formation of an insufficient level of neutralizing antibodies in vaccinated against COVID-19 patient M. and contributed to the development of a new coronavirus infection with minimal manifestations in contact with SARS-CoV-2.

scholarly journals Lack of Maternal Antibodies to P Serotypes May Predispose Neonates to Infections with Unusual Rotavirus Strains

1998 ◽  
Vol 5 (4) ◽  
pp. 527-530 ◽  
Author(s):  
Madhumati Ramachandran ◽  
Aarti Vij ◽  
Ramesh Kumar ◽  
Bimal K. Das ◽  
Jon R. Gentsch ◽  
...  
Keyword(s):  
Neutralizing Antibodies ◽  
Vaccine Candidate ◽  
Immunoglobulin A ◽  
Neutralizing Antibody ◽  
Maternal Antibodies ◽  
New Delhi ◽  
Older Children ◽  
Medical Sciences ◽  
Tetravalent Vaccine ◽  
Specific Immunoglobulin

ABSTRACT Rotavirus (RV) strains infecting newborns often have unique neutralization antigens (P serotypes) on their outer capsids that are distinct from those found on RV strains that cause diarrhea in older children. We examined the hypothesis that unusual RV strains preferentially infect newborns because the newborns lack maternal neutralizing antibodies to these strains. To test this hypothesis, sera and saliva samples collected from neonates infected with 116E-like (P[11]G9) strains in the maternity ward of the All India Institute of Medical Sciences (AIIMS) hospital in New Delhi were tested for neutralizing antibodies against common RV strains and those infecting newborns and these titers were compared with those of newborns who did not become infected (controls). The infected neonates had significantly lower levels of cord blood neutralizing antibodies to 116E than the controls, suggesting that immunity to neonatal RV infection is acquired transplacentally through maternal antibodies. Further, this study confirmed the immunogenicity of the AIIMS neonatal strain 116E, a vaccine candidate, in its ability to evoke a potent RV-specific immunoglobulin A and neutralizing antibody response in serum and saliva among the infected babies. Our findings have important implications for the development of an effective RV vaccine. In India, where G9 strains are common in the community, the use of 116E as a vaccine, together with the rhesus tetravalent vaccine, may provide a broader protection against all the circulating RV serotypes, including serotype G9, which is not represented in the current rhesus RV tetravalent vaccine (G1-G4).

Sign in / Sign up

Export Citation Format

Share Document