Pathogenicity of fibroblast- and lymphocyte-specific variants of minute virus of mice

We tested twostrains oftheminute virus ofmice(MVM)forpathogenic effects andpatterns ofinfection in laboratory mice. Thetwostrains differ intheir ability toinfect differentiated cultured cells: theprototype virus, MVMp,infects onlyfibroblasts, while itsvariant, MVMi,isrestricted tolymphocytes. We findthatneither strain hasany demonstrable effects on theT-cell function ofmiceinfected asadults. Incontrast, MVMi,but notMVMp,isable toinduce arunting syndrome accompanied bymildimmunedeficiencies upon theinfection ofnewborn mice. After neonatal infection, MVMispreads tomany organs,andthepresenceofviral replicative formDNA isevident innucleic acidhybridization experiments. Incontrast, replication ofMVMp can be detected onlybytheseroconversion ofinfected animals. Newbornmicethat grow abnormally as a result of MVMiinfection also havelowcirculating antibody titers tothevirus. Thisphenomenon may bea consequence ofthelymphotropism ofMVMi. Thegenus Parvovirus ofthefamily Parvoviridae groups a large numberofnondefective single-stranded DNA viruses that infect vertebrates (18). A characteristic feature ofthese viruses isthattheygrowinrapidly dividing tissues, being dependent fortheir ownreplication onfunctions transiently expressed during theSphase ofthecell cycle. Inaddition to this requirement, their growth seemstoberestricted toa limited numberofdifferentiated cell types. Several parvoviruses havebeenimplicated intheetiology ofsocially andeconomically important animal diseases. The syndromes associated withthese infections include fetal and neonatal death, congenital malformations, enteritis, hepatitis, myocarditis, cerebellar ataxia, hemorrhagic encephalopathy, dwarfism, andpanleukopenia (17). Recently, ahuman parvovirus (strain B-19)wasshowntobetheetiological agentoffifth disease, anerythematous rashthataffects mostly children, andoftheaplastic crises ofsickle-cell anemia patients (1). Thepathogenic effects ofthevirus can beattributed toitstropism forprecursor cells ofthe erythroid line. Theobject ofthis work, theminute virus ofmice(MVM), hasbeenstudied ingreat detail atthemolecular level asa paradigm forthegenus Parvovirus. However, its pathogenic potential inmiceremains unclear. Ithasbeenreported that intracranial injection ofMVM into newborn micecancause growth retardation andcerebellar lesions (10), butthere isno solid evidence thatinfection viamorenatural routes can causedisease. Serological evidence fromlaboratory mouse colonies suggests that MVM ishighly prevalent butpersists inaclinically inapparent state (12). Twoindependent isolates ofMVM havebeendescribed. Thefirst strain, called MVMp (for prototype), wasisolated froma murineadenovirus stockandwassubsequently adapted forgrowth inmousefibroblasts (4). Morerecently, another strain wasisolated asacontaminant ofanEL-4 T-cell lymphoma culture andwasshowntohaveaninhibi