Contributions of E1A to mouse adenovirus type 1 pathogenesis following intranasal inoculation.
We investigated the role of mouse adenovirus type 1 (MAV-1) early region 1A (E1A) protein in adenovirus respiratory infection. Intranasal (i.n.) inoculation of mice with wild type (wt) virus induced chemokine and cellular inflammatory responses in the lung. We observed similar responses in mice infected with an E1A-null mutant virus at the same dose, although the magnitude of these responses was lower. Levels of viral hexon gene expression were lower in the lung following infection with E1A-null virus than with wt virus. When input doses were adjusted so that equivalent viral loads were present following infection with varying doses of wt and E1A-null virus, we observed equivalent chemokine upregulation in the lung. Dissemination to the brain occurred following i.n. inoculation with equal doses of wt or E1A-null virus, but viral gene expression and viral loads were lower and the magnitude of chemokine responses was lower in brains of E1A-null virus-infected mice. CD4 and CD8 T cells and neutrophils were recruited to the brains of mice infected with either wt or E1A-null virus. Together, these data suggest that MAV-1 E1A makes important contributions to viral replication in the lung and the brain following i.n. inoculation. However, E1A is not essential for the induction of inflammatory responses in the lung or for viral dissemination out of the lung.
Weinberg
Jason B
JB
University of Michigan Health System, Division of Pediatric Infectious Diseases, L2225 Women's/0244, 1500 East Medical Center Drive, Ann Arbor, MI 48109-0244, USA. jbwein@umich.edu
Jensen
Daniel R
DR
Gralinski
Lisa E
LE
Lake
Amy R
AR
Stempfle
Gregory S
GS
Spindler
Katherine R
KR
D000256:Adenoviridae / Q000472:pathogenicity* / Q000502:physiology; D000257:Adenoviridae Infections / Q000276:immunology* / Q000473:pathology / Q000821:virology*; D017500:Adenovirus E1A Proteins / Q000502:physiology*; D000818:Animals; D000956:Antigens, Viral / Q000235:genetics; D001921:Brain / Q000276:immunology / Q000821:virology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D036022:Capsid Proteins / Q000235:genetics; D002460:Cell Line; D018925:Chemokines / Q000096:biosynthesis / Q000235:genetics; D015870:Gene Expression; D007249:Inflammation / Q000473:pathology; D008168:Lung / Q000276:immunology / Q000821:virology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009504:Neutrophils / Q000382:microbiology; D012141:Respiratory Tract Infections / Q000276:immunology* / Q000473:pathology / Q000821:virology*; D019562:Viral Load; D014779:Virus Replication
D017500:Adenovirus E1A Proteins; D000956:Antigens, Viral; D036022:Capsid Proteins; D018925:Chemokines; C018315:hexon capsid protein, Adenovirus