Parvovirus B19-Induced Apoptosis of Hepatocytes

Abstract

Parvovirus B19 (B19 virus) can persist in multiple tissues and has been implicated in a variety of diseases, including acute fulminant liver failure. The mechanism by which B19 virus induces liver failure remains unknown. Hepatocytes are nonpermissive for B19 virus replication. We previously reported that acute fulminant liver failure associated with B19 virus infection was characterized by hepatocellular dropout. We inoculated both primary hepatocytes and the hepatocellular carcinoma cell line Hep G2 with B19 virus and assayed for apoptosis by using annexin V staining. Reverse transcriptase PCR analysis and immunofluorescence demonstrated that B19 virus was able to infect the cells and produce its nonstructural protein but little or no structural capsid protein. Infection with B19 virus induced means of 28% of Hep G2 cells and 10% of primary hepatocytes to undergo apoptosis, which were four-and threefold increases, respectively, over background levels. Analysis of caspase involvement showed that B19 virus-inoculated cultures had a significant increase in the number of cells with active caspase 3. Inhibition studies demonstrated that caspases 3 and 9, but not caspase 8, are required for B19 virus-induced apoptosis.Parvovirus B19 (B19 virus) is the only parvovirus known to cause disease in humans. It is a small, single-stranded DNA virus that is transmitted in blood products or through aerosols and fomite contamination. B19 virus infection in children typically manifests as erythema infectiosum (fifth disease). Infection of adults frequently leads to arthropathy. In patients with chronic hemolytic anemias, such as sickle cell disease or hereditary spherocytosis, B19 virus infection causes transient aplastic crisis by destroying the erythroid precursor pool (34). Although these are the best-described clinical illnesses induced by B19 virus, the virus has been implicated in a wide spectrum of other illnesses.Acute fulminant liver failure (AFLF) is a potentially fatal disease that may occur as a result of hepatic infection, toxic damage, or liver transplantation complications. Over one-third of idiopathic AFLF cases are accompanied by aplastic crisis (6). Langnas and colleagues demonstrated that a significant number of patients with AFLF associated with aplastic anemia had parvovirus B19 virus DNA in the native liver that was detectable by PCR (18). Karetnyi et al. demonstrated the presence of active B19 virus infection, as indicated by the presence of viral RNA, in AFLF associated with aplastic anemia. Interestingly, although RNA was detected, replicative forms of the viral genome were not, suggesting active infection without replication of the virus in these tissues (16). Hepatocytes express globoside, the receptor for B19 virus, and empty capsids will bind to extracts from liver tissue (9). Other diseases associated with B19 virus infection include arthropathy (32, 34), myocarditis (36), encephalitis (11), hepatitis (42), dermatomyositis (7), and scleroderma (22). Cooling and coworkers showed a link between tissu...

The Genome of Human Parvovirus B19 Can Replicate in Nonpermissive Cells with the Help of Adenovirus Genes and Produces Infectious Virus

“…Our results also support the previous observation that the B19V P6 promoter is cell type specific, transcribing actively in EPCs and myeloid cell lines (15,44) but poorly in epithelial cell types other than 293 cells (15,31). Previous studies suggested that HepG2 and HMEC-1 cells could be infected by B19V (14,32). However, our data indicate that this infectivity is unlikely.…”

Acute Hepatitis as a Manifestation of Parvovirus B19 Infection

“…Hepatic cell damage related to direct viral invasion is one possibility (1,9). Alternatively, injury may result as an indirect consequence of the immune response directed against the virus (1).…”

Bioportfolio: Lifelong persistence of variant and prototypic erythrovirus DNA genomes in human tissue

“…Serodiagnostics (i.e., IgG seropositivity; IgG avidity, IgG epitope type specificity, and the absence of IgM ruling out recent primary infection) verified the specificity of the original findings and showed the DNA persistence in synovium to be long (24,27). Besides revolutionizing the diagnostic criteria of parvovirus arthropathy (28,29), the tissue persistence has evoked wide interest in the possible etiopathogenic role of these viruses in inflammatory and other chronic diseases (30)(31)(32)(33)(34)(35)(36). However, the substantial span of the viral genome persistence as well as its cellular and molecular mechanisms remained undefined.…”