Localization of Hepatitis A Antigen in Marmoset Organs during Acute Infection with Hepatitis A Virus

Mathiesen, Lars; Drucker, J; Lorenz, Douglas E.; Wagner, J; Gerety, Robert J.; Purcell, Robert H.

doi:10.1093/infdis/138.3.369

Cited by 91 publications

(42 citation statements)

References 16 publications

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“…Experimental models of HAV infection have been produced in both chimpanzees [Maynard et al, 1975;Dienstag et al, 19751 and tamarins [Mathieson et al, 1978;Krawczynski et al, 1981;Karayannis et al, 19861, and these models have led to a more complete understanding of the natural history and pathogenesis of this infection. The mechanism(s) of hepatocyte injury during HAV infection, however, is unknown.…”

Section: Introductionmentioning

confidence: 99%

Appearance of immune complexes during experimental hepatitis A infection in chimpanzees

Margolis

Nainan

Krawczynski

et al. 1988

Journal of Medical Virology

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Circulating immune complexes (CICs) were detected during the course of experimental hepatitis A virus (HAV) infection in 8 of 9 chimpanzees. In all cases, the predominant class of antibody detected in the CIC was IgM. The appearance of IgM-CIC usually preceded the onset of liver enzyme elevations, and in all instances, the appearance of IgM-CIC correlated with the presence of IgM anti-HAV. Six of 8 animals tested had significant depression of C3 concentrations during the course of infection, and this depression occurred at the peak of CIC activity. Immunohistologic studies demonstrated granular deposits of IgM localized in sinusoidal cells during peak of IgM-CIC activity. IgM-CICs appear to be a fairly consistent finding during HAV infection and probably represent the viremic phase of the disease. However, they do not appear to mediate hepatocellular injury by direct action on hepatocytes.

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Section: Introductionmentioning

confidence: 99%

Appearance of immune complexes during experimental hepatitis A infection in chimpanzees

Margolis

Nainan

Krawczynski

et al. 1988

Journal of Medical Virology

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“…Although it is well established that HAV is transmitted through the fecal-oral route, it is unknown whether there is a primary site of HAV replication in the digestive system or whether the input virus is transported to the blood and then reaches the liver, its target organ (45). HAV initially infects Kupffer cells, which are liver-resident macrophages, and then extends to the hepatocytes (2,25,42). We have previously shown that HAVCR1/TIM1 is a receptor for HAV (13,19), but the exact role of this receptor in the pathogenesis of HAV needs to be fully elucidated.…”

Section: Discussionmentioning

confidence: 99%

Immunoglobulin A (IgA) Is a Natural Ligand of Hepatitis A Virus Cellular Receptor 1 (HAVCR1), and the Association of IgA with HAVCR1 Enhances Virus-Receptor Interactions

Tami

Silberstein

Manangeeswaran

et al. 2007

J Virol

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The hepatitis A virus (HAV) cellular receptor 1 (HAVCR1/ TIM1) is a type 1 integral membrane glycoprotein consisting of a characteristic six-cysteine immunoglobulin (Ig)-like domain extended above the cell surface by a mucin-like domain that contains a variable number of threonine, serine, and proline (TSP) hexameric repeats (19). The monkey (19) and human (13) HAVCR1/TIM1 were the first identified members of the T-cell immunoglobulin mucin (TIM) family, an immunologically important group of receptors (22,28,29,32) that is conserved in vertebrates. Although HAV is a hepatotropic virus that causes acute hepatitis in humans, infection with HAV has been shown to greatly reduce the risk of developing asthma and allergy in humans (26,27). Because the gene encoding HAVCR1/TIM1 has been shown to be an important asthma and allergy susceptibility gene in humans (14,15,29,30), it appears that HAVCR1/TIM1 plays a critical role in regulating T-cell differentiation (29) and the development of atopy (30). However, the precise immunological mechanisms by which HAV infection prevents atopy and the exact mechanisms by which HAVCR1/TIM1 functions normally in the absence of HAV infection to regulate immune responses are not fully understood.In mice, Tim-1 has been shown to be an important T-cell costimulatory molecule, which is preferentially expressed on T helper 2 (Th2) cells (48). Cross-linking of mouse Tim-1 enhances T-cell proliferation and cytokine production and prevents the induction of respiratory tolerance, resulting in airway hyperreactivity, a cardinal feature of asthma (48). Tim-1 costimulation requires its cytoplasmic tail and a conserved tyrosine that can be phosphorylated (8). In humans, HAVCR1/TIM1 is expressed in Th2 cell lines, is associated with remission in patients with multiple sclerosis (21), and is highly expressed in kidneys (19) primarily after injury (16) or in tumors (50). Recently, mouse Tim-4, a TIM family member expressed on antigen-presenting cells (APCs), has been shown to be a ligand for Tim-1 (31). However, whether human TIM4, the ortholog of mouse Tim-4, functions as a ligand of human HAVCR1/ TIM1 is not known.Using an expression cloning strategy with a soluble form of the HAVCR1/TIM1 containing the HAVCR1/TIM1 Ig variable-like (IgV) region fused to the Fc fragment of a human IgG1 antibody [HAVCR1/TIM1(IgV)-Fc], we identified IgA as a specific ligand of HAVCR1/TIM1. The interaction between HAVCR1/TIM1 and IgA is specific, since it was blocked with monoclonal antibody (MAb) to immunoglobulin alpha 1 heavy (Ig␣1) or lambda light (Ig) chain, with anti-

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“…In 1971, Combes et al [26] described the first case in which Australian antigen was likely the responsible agent for the development of glomerulonephritis in a patient with hepatitis B infection. Mathiesen et al [27] was the first to detect hepatitis A antigen in the glomeruli of kidney in marmoset in the acute phase of infection after intravenous inoculation with hepatitis A virus. The fluorescence in the glomeruli appeared to be distributed along the basement membrane in a pattern suggestive of immune complex deposition.…”

Section: Discussionmentioning

confidence: 99%

Acute Anuric Renal Failure in Nonfulminant Hepatitis A Infection

Jamil

Massry²

1998

Am J Nephrol

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Acute renal failure has recently been recognized as a rare complication of nonfulminant hepatitis A infection. The availability of a specific test for IgM antibody to hepatitis A should permit prompt diagnosis of the disease and a better evaluation of its association with acute renal failure. The exact mechanism for acute renal failure in hepatitis A is uncertain but glomerulonephritis, acute tubular necrosis and hepatorenal syndrome have been postulated. We report a patient with hepatitis A infection and acute renal failure most likely due to acute tubular necrosis.

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Localization of Hepatitis A Antigen in Marmoset Organs during Acute Infection with Hepatitis A Virus

Cited by 91 publications

References 16 publications

Appearance of immune complexes during experimental hepatitis A infection in chimpanzees

Appearance of immune complexes during experimental hepatitis A infection in chimpanzees

Immunoglobulin A (IgA) Is a Natural Ligand of Hepatitis A Virus Cellular Receptor 1 (HAVCR1), and the Association of IgA with HAVCR1 Enhances Virus-Receptor Interactions

Acute Anuric Renal Failure in Nonfulminant Hepatitis A Infection

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