A rat cytomegalovirus strain with a disruption of the r144 MHC class I-like gene is attenuated in the acute phase of infection in neonatal rats.
We previously generated an RCMV strain in which the r144 gene, encoding a major histocompatibility complex class I homolog, had been deleted (RCMVdelta r144). To investigate the role of r144 during acute infection of neonatal rats, we infected three days-old neonatal rats with either RCMVdelta r144 or wild type (wt) RCMV and the presence of infectious virus as well as viral DNA in various organs was determined at either 3, 5 or 21 days p.i.. In addition, we assessed both type and number of inflammatory cells in these organs. Interestingly, a significantly lower concentration of infectious virus as well as viral DNA was found in spleens of RCMVdelta r144-infected rats than in those of wt RCMV-infected animals at 3 days p.i.. At the same time point, a significantly lower amount of infiltrating NK cells and monocytes/macrophages was seen in the spleens of RCMVdelta r144-infected rats than in spleens of rats infected with wt RCMV. At 21 days p.i., RCMVdelta r144-infected rats were found to have lower virus titers in the salivary glands than wt RCMV-infected animals. Significant differences between RCMVdelta r144- and wt RCMV-infected rats were detected neither at other time points nor at other sites. We conclude that after infection of neonatal rats, the replication of RCMVdelta r144 is severely restricted compared to wt RCMV.
Kloover
J S
JS
Department of Medical Microbiology, Cardiovascular Research Institute Maastricht, University of Maastricht, The Netherlands.
Grauls
G E L M
GE
Blok
M J
MJ
Vink
C
C
Bruggeman
C A
CA
D000208:Acute Disease; D000818:Animals; D000831:Animals, Newborn; D002452:Cell Count; D004279:DNA, Viral / Q000032:analysis; D004195:Disease Models, Animal; D005260:Female; D017353:Gene Deletion; D005805:Genes, MHC Class I / Q000235:genetics*; D006566:Herpesviridae Infections / Q000276:immunology / Q000821:virology*; D007962:Leukocytes / Q000821:virology; D008264:Macrophages / Q000821:virology; D008297:Male; D018146:Muromegalovirus / Q000737:chemistry / Q000235:genetics*; D051381:Rats; D012469:Salivary Glands / Q000821:virology; D013154:Spleen / Q000276:immunology / Q000821:virology; D013997:Time Factors; D014764:Viral Proteins / Q000235:genetics*
D004279:DNA, Viral; D014764:Viral Proteins; C403496:r144 protein, Cytomegalovirus