Molecular and structural basis of the evolution of parvovirus tropism.
Parvoviruses have small genomes and, consequently, are highly dependent on their host for various functions in their reproduction. Since these viruses generally use ubiquitous receptors, restrictions are usually intracellularly regulated. A lack of mitosis, and hence absence of enzymes required for DNA replication, is a powerful block of virus infection. Allotropic determinants have been identified for several parvoviruses: porcine parvovirus, canine parvovirus (CPV), feline parvovirus (feline panleukopenia virus), minute virus of mice, Aleutian disease virus, and GmDNV (an insect parvovirus). Invariably, these identifications involved the use of infectious clones of these viruses and the exchange of restriction fragments to create chimeric viruses, of which the resulting phenotype was then established by transfection in appropriate cell lines. The tropism of these viruses was found to be governed by minimal changes in the sequence of the capsid proteins and, often, only 2 or 3 critical amino acids are responsible for a given tropism. These amino acids are usually located on the outside of the capsid near or on the spike of the threefold axis for the vertebrate parvoviruses and on loops 2 or 3 for the insect parvoviruses. This tropism is not mediated via specific cellular receptors but by interactions with intracellular factors. The nature of these factors is unknown but most data point to a stage beyond the conversion of the single-stranded DNA genome by host cell DNA polymerase into monomeric duplex intermediates of the replicative form. The sudden and devastating emergence of mink enteritis virus (MEV) and CPV in the last 50 years, and the possibility of more future outbreaks, demonstrates the importance of understanding parvovirus tropism.
Tijssen
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Laboratory of Structural and Molecular Virology, INRS-Institut Armand-Frappier, Université du Québec, Laval, Canada. peter_tijssen@iaf.uquebec.ca
D000818:Animals; D002415:Cats; D003198:Computer Simulation; D004285:Dogs; D051379:Mice; D017992:Parvovirus / Q000254:growth & development* / Q000502:physiology; D013329:Structure-Activity Relationship; D018523:Tropism; D014779:Virus Replication