Contributions of E1A to mouse adenovirus type 1 pathogenesis following intranasal inoculation

Department of Microbiology and Immunology, University of Michigan, Ann Arbor, Michigan, United States
Virology (Impact Factor: 3.28). 02/2007; 357(1):54-67. DOI: 10.1016/j.virol.2006.08.013
Source: PubMed

ABSTRACT 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.


Available from: Lisa E Gralinski, May 15, 2014
  • [Show abstract] [Hide abstract]
    ABSTRACT: This paper presents a modelling and experimental study on an H-shaped ferrite core electromagnetic sensor for phase transformation detection in steel rolling and controlled cooling applications. It has been found that the response of the H-shaped sensor after normalisation can be described by a simple analytical model. Further, it has been found that the zero-crossing frequency for the real part of the inductance spectra and the peak frequency of the imaginary part of the inductance spectra are linearly proportional to the magnetic permeability of the steel strip under test. These findings are helpful in understanding the response of the EM sensor in an industrial set-up and possibly lead to more accurate determination of steel magnetic properties and hence characterise the micro-structural properties.
    NDT & E International 11/2011; 44(7):547-552. DOI:10.1016/j.ndteint.2011.05.005 · 1.72 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Mouse adenovirus type 1 (MAV-1) causes acute and persistent infections in mice, with high levels of virus found in the brain, spinal cord and spleen in acute infections. MAV-1 infects endothelial cells throughout the mouse, and monocytes/macrophages have also been implicated as targets of the virus. Here we determined the extent and functional importance of macrophage infection by MAV-1. Bone marrow-derived macrophages expressed MAV-1 mRNAs and proteins upon ex vivo infection. Adherent peritoneal macrophages from infected mice expressed viral mRNAs and produced infectious virus. Infected chemokine (C–C motif) receptor 2 (CCR2) knockout mice, which are defective for macrophage recruitment, did not show differences in survival or MAV-1 load compared to controls. In contrast, macrophage depletion using clodronate-loaded liposomes resulted in increased virus replication in spleens of a MAV-1-resistant mouse strain, BALB/cJ. Thus macrophages serve both as targets of infection and as effectors of the host response.
    Virology 08/2009; 390(2-390):307-314. DOI:10.1016/j.virol.2009.05.025 · 3.28 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Respiratory viruses cause substantial disease and are a significant healthcare burden. Virus-induced inflammation can be detrimental to the host, causing symptoms during acute infection and leading to damage that contributes to long-term residual lung disease. Prostaglandin E2 (PGE2) is a lipid mediator that is increased in response to many viral infections, and inhibition of PGE2 production during respiratory viral infection often leads to a decreased inflammatory response. We tested the hypothesis that PGE2 promotes inflammatory responses to mouse adenovirus type 1 (MAV-1) respiratory infection. Acute MAV-1 infection increased COX-2 expression and PGE2 production in wild type mice. Deficiency of the E prostanoid 2 receptor had no apparent effect on MAV-1 pathogenesis. Virus-induced induction of PGE2, IFN-γ, CXCL1, and CCL5 was reduced in mice deficient in microsomal PGE synthase-1 (mPGES-1(-/-) mice). However, there were no differences between mPGES-1(+/+) and mPGES-1(-/-) mice in viral replication, recruitment of leukocytes to airways or lung inflammation. Infection of both mPGES‑1(+/+) and mPGES-1(-/-) mice led to protection against reinfection. Thus, while PGE2 promotes the expression of a variety of cytokines in response to acute MAV-1 infection, PGE2 synthesis does not appear to be essential for generating pulmonary immunity.
    PLoS ONE 10/2013; 8(10):e77628. DOI:10.1371/journal.pone.0077628 · 3.53 Impact Factor