Hepatitis A Virus Attachment to Cultured Cell Lines

Stapleton, Jack T.; Frederick, John; Meyer, Barbara C.

doi:10.1093/infdis/164.6.1098

Cited by 34 publications

(23 citation statements)

References 24 publications

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“…Considerable evidence suggests that the immunodominant neutralizing antigenic site of HAV is in VP3 (2). The present result is consistent with previous evidence indicating that the immunodominant neutralization antigenic site of HAV is not directly involved in cell attachment (35).…”

Section: Discussionsupporting

confidence: 92%

Capsid Functions of Inactivated Human Picornaviruses and Feline Calicivirus

Nuanualsuwan

Cliver

2003

Appl Environ Microbiol

161

135

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The exceptional stability of enteric viruses probably resides in their capsids. The capsid functions of inactivated human picornaviruses and feline calicivirus (FCV) were determined. Viruses were inactivated by UV, hypochlorite, high temperature (72°C), and physiological temperature (37°C), all of which are pertinent to transmission via food and water. Poliovirus (PV) and hepatitis A virus (HAV) are transmissible via water and food, and FCV is the best available surrogate for the Norwalk-like viruses, which are leading causes of food-borne and waterborne disease in the United States. The capsids of all 37°C-inactivated viruses still protected the viral RNA against RNase, even in the presence of proteinase K, which contrasted with findings with viruses inactivated at 72°C. The loss of ability of the virus to attach to homologous cell receptors was universal, regardless of virus type and inactivation method, except for UV-inactivated HAV, and so virus inactivation was almost always accompanied by the loss of virus attachment. Inactivated HAV and FCV were captured by homologous antibodies. However, inactivated PV type 1 (PV-1) was not captured by homologous antibody and 37°C-inactivated PV-1 was only partially captured. The epitopes on the capsids of HAV and FCV are evidently discrete from the receptor attachment sites, unlike those of PV-1. These findings indicate that the primary target of UV, hypochlorite, and 72°C inactivation is the capsid and that the target of thermal inactivation (37°C versus 72°C) is temperature dependent.

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Section: Discussionsupporting

confidence: 92%

Capsid Functions of Inactivated Human Picornaviruses and Feline Calicivirus

Nuanualsuwan

Cliver

2003

Appl Environ Microbiol

161

135

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“…Attachment of HAV to cell surface receptors is enhanced by the presence of calcium ions, prompting speculation that calcium can cause minor conformational changes in HAV particles, mediating a stronger virus-receptor interaction [49][50][51]. In light of these data, the effect of calcium ions on HAV stability was examined.…”

Section: Effect Of Calcium Ions On Hav Infectivitymentioning

confidence: 99%

Examination of Potential Inhibitors of Hepatitis A Virus Uncoating

Bishop¹

1998

Intervirology

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Hepatitis A virus (HAV) replication in BS-C-1 cells was studied in the presence of ten potential uncoating inhibitors. Strong inhibition of HAV replication was only observed in the presence of the phenothiazine compound chlorpromazine and the lysosomotropic agent chloroquine, but not by other lysosomotropic agents. Chlorpromazine and chloroquine were found to prevent virus uncoating. Chlorpromazine is known to inhibit endocytosis of non- clathrin-coated vesicles. Chloroquine is a weak base amine, and thought to inhibit virus replication by preventing endosomal acidification. These results therefore suggest that entry of HAV in BS-C-1 cells does not depend on the low pH encountered in the clathrin-coated endocytic entry pathway. A possible role of calcium ions in mediating viral uncoating is discussed, as calcium ions were found to destabilize HAV particles in vitro.

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“…Infection results in life-long immunity, and several highly effective vaccines based on inactivated virus are available, the use of which has dramatically reduced the incidence of hepatitis A, largely in developed countries such as the United States (15,18,72,78). Although HAV has been shown to infect enterocyte-derived cells in culture (4,59), very little or no virus is detectable in the gastrointestinal cells of experimentally infected animals (1,34). Viral replication predominantly occurs in hepatocytes: the likely source of both the significant acute-phase viremia and the high titers of virus found in feces which are responsible for transmission to new hosts.…”

mentioning

confidence: 99%

Vectorial Entry and Release of Hepatitis A Virus in Polarized Human Hepatocytes

Snooks

Bhat

Mackenzie

et al. 2008

J Virol

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Hepatitis A virus (HAV) is an enterically transmitted virus that replicates predominantly in hepatocytes within the liver before excretion via bile through feces. Hepatocytes are polarized epithelial cells, and it has been assumed that the virus load in bile results from direct export of HAV via the apical domain of polarized hepatocytes. We have developed a subclone of hepatocyte-derived HepG2 cells (clone N6) that maintains functional characteristics of polarized hepatocytes but displays morphology typical of columnar epithelial cells, rather than the complex morphology that is typical of hepatocytes. N6 cells form microcolonies of polarized cells when grown on glass and confluent monolayers of polarized cells on semipermeable membranes. When N6 microcolonies were exposed to HAV, infection was restricted to peripheral cells of polarized colonies, whereas all cells could be infected in colonies of nonpolarized HepG2 cells (clone C11) or following disruption of tight junctions in N6 colonies with EGTA. This suggests that viral entry occurs predominantly via the basolateral plasma membrane, consistent with uptake of virus from the bloodstream after enteric exposure, as expected. Viral export was also found to be markedly vectorial in N6 but not C11 cells. However, rather than being exported from the apical domain as expected, more than 95% of HAV was exported via the basolateral domain of N6 cells, suggesting that virus is first excreted from infected hepatocytes into the bloodstream rather than to the biliary tree. Enteric excretion of HAV may therefore rely on reuptake and transcytosis of progeny HAV across hepatocytes into the bile. These studies provide the first example of the interactions between viruses and polarized hepatocytes.

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Hepatitis A Virus Attachment to Cultured Cell Lines

Cited by 34 publications

References 24 publications

Capsid Functions of Inactivated Human Picornaviruses and Feline Calicivirus

Capsid Functions of Inactivated Human Picornaviruses and Feline Calicivirus

Examination of Potential Inhibitors of Hepatitis A Virus Uncoating

Vectorial Entry and Release of Hepatitis A Virus in Polarized Human Hepatocytes

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