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Involvement of viruses in human neurodegenerative diseases and the underlying pathologic mechanisms remain generally unclear. Human respiratory coronaviruses (HCoV) can infect neural cells, persist in human brain, and activate myelin-reactive T cells. As a means of understanding the human infection, we characterized in vivo the neurotropic and neuroinvasive properties of HCoV-OC43 through the development...
The CC chemokine ligand 2 (CCL2, monocyte chemoattractant protein-1) is important in coordinating the immune response following microbial infection by regulating T cell polarization as well as leukocyte migration and accumulation within infected tissues. The present study examines the consequences of mouse hepatitis virus (MHV) infection in mice lacking CCL2 (CCL2 −/− ) in order to determine...
Respiratory syncytial virus (RSV) is worldwide the single most important respiratory pathogen in infancy and early childhood. The G glycoprotein of RSV, named attachment protein, is produced by RSV-infected lung epithelial cells in both a membrane-anchored (mG protein) and a soluble form (sG protein) that is secreted by the epithelial cell. Currently, the biological role of the sG protein in primary...
Sensitized CD4 + T cells play an essential role in delayed type hypersensitivity (DTH) elicited by HSV-1 antigen. As activated CD4 + T cells express CXCR3, we investigated whether this chemokine receptor was involved in their recruitment. Antibody blockade of CXCR3 suppressed DTH, whereas ear pinna swelling was not impaired in mice lacking the gene for CCR5, another frequently expressed...
Studies of the pathogenesis of adenovirus respiratory disease are limited by the strict species-specificity of the adenoviruses. Following intranasal inoculation of adult C57BL/6 mice with mouse adenovirus type 1 (MAV-1), we detected MAV-1 early region 3 (E3) and hexon gene expression in the lungs at 7 days post-infection (dpi). We detected MAV-1 E3 protein in the respiratory epithelium at 7 dpi....
Prostaglandins (PGs) are lipid mediators that participate in the regulation of immunological and inflammatory responses, and PG production can affect viral replication. In this study, we have investigated the mechanism of PGE2 production in airway epithelial cells, following respiratory syncytial virus (RSV) infection, and its role in viral replication. We show that RSV infection strongly induces...
Macrophages are pivotal for the regulation of immune and inflammatory responses, but whether their role in HIV infection is protective or deleterious remains unclear. In this study, we investigated the effect of pro- and anti-inflammatory stimuli on macrophage sensitivity to two different aspects of HIV infection: their susceptibility to infection stricto sensu, which we measured by endpoint titration...
We explore relationships linking clinical symptoms, respiratory dysfunction, and local production of proinflammatory chemokines in the pneumonia virus of mice (PVM) model of viral bronchiolitis. With a reduced inoculum of this natural rodent pathogen, we observe virus clearance by day 9, while clinical symptoms and respiratory dysfunction persist through days 14 and 17 postinoculation, respectively...
Respiratory syncytial virus (RSV)-induced chemokine gene expression occurs through the activation of a subset of transcription factors, including Interferon Regulatory Factor (IRF)-3. In this study, we have investigated the signaling pathway leading to RSV-induced IRF-3 activation and whether it is mediated by intracellular reactive oxygen species (ROS) generation. Our results show that RSV infection...
Myxoma virus (MYX) prevents apoptosis in RK-13 cells and forms thick dermal lesions with 100% mortality in rabbits. MYX encodes the virulence factor SERP2, a serine proteinase inhibitor (serpin). SERP2 was mutated to evaluate SERP2 function during MYX infection. MYXΔSERP2::lacZ (deleted for SERP2) did not inhibit apoptosis in RK-13 cells; infected rabbits had thin dermal lesions and <10% mortality...
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...
RNase L helps mediate the antiviral state induced by type I interferons (IFNαβ). Although herpes simplex virus (HSV) encodes inhibitors of the IFNαβ-induced antiviral response, the IFNαβ system serves the body as a first line of defense against HSV. We investigated whether RNase L limits HSV-2 replication and virulence. RNaseL −/− and wild-type C57BL/6 mice were infected intravaginally with...
High levels of interleukin-6 (IL-6) in the acute stage associated with lung lesions were found in SARS patients. To evaluate the mechanisms behind this event, we investigated the roles of SARS-CoV proteins in the regulation of IL-6. Results showed that the viral nucleocapsid (N) protein activated IL-6 expression in a concentration-dependent manner. Promoter analyses suggested that NF-κB binding element...
Human metapneumovirus (hMPV) is a major cause of lower respiratory tract infections (LRTIs) in infants, elderly and immunocompromised patients. In this study, we show that hMPV can infect in a similar manner epithelial cells representative of different tracts of the airways. hMPV-induced expression of chemokines IL-8 and RANTES in primary small alveolar epithelial cells (SAE) and in a human alveolar...
Immune responses to virus infection undergo significant change as part of the aging process. Here we examine the inflammatory responses of older, but otherwise immunologically naive mice to infection with pneumonia virus of mice (PVM). Although we see no changes in the extent or kinetics of virus replication, we observe diminished local production of inflammatory mediators, including MIP-1α, JE/MCP-1,...
Hepatitis C virus (HCV) causes chronic hepatitis, which often results in the development of liver cirrhosis and hepatocellular carcinoma (HCC) worldwide. In this study, we demonstrated that the non-structural protein NS3 of HCV enhances cyclooxygenase-2 (COX-2) gene promoter activity, COX-2 mRNA expression, COX-2 protein production, and prostaglandin E2 (PGE2) release in HepG2 cells in a concentration-dependent...
Mice infected with coxsackievirus B1 Tucson (CVB1 T ) develop chronic, post-viral myopathy (PVM) with clinical manifestations of hind limb muscle weakness and myositis. The objective of the current study was to establish the genetic basis of myopathogenicity in CVB1 T . Using a reverse genetics approach, full attenuation of PVM could only be achieved by simultaneously mutating four...
Human metapneumovirus (hMPV) is a major cause of lower respiratory tract infections in infants, elderly and immunocompromised patients. Little is known about the response to hMPV infection of airway epithelial cells, which play a pivotal role in initiating and shaping innate and adaptive immune responses. In this study, we analyzed the transcriptional profiles of airway epithelial cells infected with...
Human Adenovirus Type 4 (HAdV-4) is responsible for epidemic outbreaks of Acute Respiratory Disease (especially in military recruits), and is known to cause significant morbidity with several reported cases of mortality. However, we do not understand why this serotype causes such high morbidity, and have little insight into the immunobiology of HAdV-4 infections. We have now developed a replication...
The role that interferon-γ (IFNγ) plays during herpetic stromal keratitis (HSK) has not been definitively determined. In primary HSK most reports suggest that IFNγ may help control viral replication and contribute to corneal pathology. However, its role in recurrent HSK has not been directly addressed. The present study addresses its role in recurrent HSK by comparing HSK in latently infected normal...
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