Effects of promyelocytic leukemia protein on virus-host balance Journal Article


Authors: Bonilla, W. V.; Pinschewer, D. D.; Klenerman, P.; Rousson, V.; Gaboli, M.; Pandolfi, P. P.; Zinkernagel, R. M.; Salvato, M. S.; Hengartner, H.
Article Title: Effects of promyelocytic leukemia protein on virus-host balance
Abstract: The cellular promyelocytic leukemia protein (PML) associates with the proteins of several viruses and in some cases reduces viral propagation in cell culture. To examine the role of PML in vivo, we compared immune responses and virus loads of PML-deficient and control mice infected with lymphocytic choriomeningitis virus (LCMV) and vesicular stomatitis virus (VSV). PML-/- mice exhibited accelerated primary footpad swelling reactions to very-low-dose LCMV, higher swelling peaks upon high-dose inoculation, and higher viral loads in the early phase of systemic LCMV infection. T-cell-mediated hepatitis and consequent mortality upon infection with a hepatotropic LCMV strain required 10- to 100-times-lower inocula despite normal cytotoxic T-lymphocyte reactivity in PML-/- mice. Furthermore, PML deficiency rendered mice 10 times more susceptible to lethal immunopathology upon intracerebral LCMV inoculation. Accordingly, 10-times-lower VSV inocula elicited specific neutralizing-antibody responses, a replication-based effect not observed with inactivated virus or after immunization with recombinant VSV glycoprotein. These in vivo observations corroborated our results showing more virus production in PML-/- fibroblasts. Thus, PML is a contributor to innate immunity, defining host susceptibility to viral infections and to immunopathology.
Keywords: infection; virus; cells; mhc class-i; lymphocytic choriomeningitis virus; persistence; viral; cytotoxic t-lymphocytes; hepatitis-b; nuclear-bodies; pml protein; growth-suppressor
Journal Title: Journal of Virology
Volume: 76
Issue: 8
ISSN: 0022-538X
Publisher: American Society for Microbiology  
Date Published: 2002-04-01
Start Page: 3810
End Page: 3818
Language: English
ACCESSION: WOS:000174520600024
DOI: 10.1128/jvi.76.8.3810-3818.2002
PROVIDER: wos
PMCID: PMC136073
PUBMED: 11907221
Notes: Article -- Source: Wos
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  1. Mirella P Gaboli
    19 Gaboli