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The viral determinants of alphavirus-induced rheumatic disease have not been elucidated. We identified an RRV strain (DC5692) which, in contrast to the T48 strain, does not induce musculoskeletal inflammation in a mouse model of RRV disease. Substitution of the RRV T48 strain nonstructural protein 1 (nsP1) coding sequence with that from strain DC5692 generated a virus that was attenuated in vivo despite...
The ORF3 protein of the pathogenic porcine circovirus 2 (PCV2) causes apoptosis of the virus-infected cells. In PCV2-infected piglets, ORF3 induces B and CD4 T lymphocyte depletion and lymphoid organ destruction and the ORF3-deficient PCV2 is attenuated in its pathogenicity (Virology, 383 (2009), 338). In addition to its role in causing the apoptosis of the immune cells, characteristic of the PCV2...
The mechanisms used by baculoviruses to exit the midgut and cause systemic infection of their insect hosts have been debated for decades. After being ingested, baculoviruses reach the midgut, where several host barriers need to be overcome in order to establish successful infection. One of these barriers is the basal lamina, a presumably virus-impermeable extracellular layer secreted by the epithelial...
The complement system functions as an immune surveillance system that rapidly responds to infection. Activation of the complement system by specific recognition pathways triggers a protease cascade, generating cleavage products that function to eliminate pathogens, regulate inflammatory responses, and shape adaptive immune responses. However, when dysregulated, these powerful functions can become...
Infection of host cells by a variety of viruses results in programmed cell death or apoptosis. In many cases, early events in virus replication that occur prior to synthesis of viral proteins and replication of viral genomes directly or indirectly activate signaling pathways that culminate in cell death. Using examples of viruses for which prodeath signaling is better defined, this review will describe...
The function of the lectin pathway of complement activation in vivo against West Nile virus (WNV) or many other pathogenic viruses has not been defined. Mice deficient in lectin pathway recognition molecules (mannose binding lectin-A (MBL-A) and mannose binding lectin-C (MBL-C)) or the effector enzyme mannan-binding lectin-associated serine protease-2 (MASP-2), were more vulnerable to WNV infection...
Data from limited autopsies of human patients demonstrate that pathological changes in EV71-infected fatal cases are principally characterized by clear inflammatory lesions in different parts of the CNS; nearly identical changes were found in murine, cynomolgus and rhesus monkey studies which provide evidence of using animal models to investigate the mechanisms of EV71 pathogenesis. Our work uses...
Experimental mouse models were used to compare virulence and reproduction rate of three mouse-adapted variants of the PR8 influenza A virus strain. We observed large differences in pathogenicity in two mouse strains. The PR8M variant was lethal in DBA/2J mice but not in C57BL/6J mice, whereas PR8F and hvPR8 variants were lethal in both mouse strains. High lethality of PR8M in DBA/2J correlated with...
Here we show that IQGAP1, a cellular protein that plays a pivotal role as a regulator of the cytoskeleton interacts with Classical Swine Fever Virus (CSFV) Core protein. Sequence analyses identified residues within CSFV Core protein (designated as areas I, II, III and IV) that maintain homology to regions within the matrix protein of Moloney Murine Leukemia Virus (MMLV) that mediate binding to IQGAP1...
Immunopathology during early simian retrovirus type 2 (SRV-2) infection is poorly characterized. Here, viral dynamics, immune response and disease progression in transiently- or persistently-infected cynomolgus macaques are assessed. Viral nucleic acids were detected in selected lymphoid tissues of both persistently- and transiently-infected macaques, even after viral clearance from the periphery...
Human infections with highly pathogenic H5N1 avian influenza viruses continue to occur in many parts of the world and pose a considerable public health threat. With the use of animal models, the identification of virulence determinants has been instrumental in improving our understanding of how these viruses cause severe disease in humans. Two genetically similar H5N1 viruses (A/Thailand/16/2004 and...
Canine influenza virus (CIV) is an emerging pathogen that causes acute respiratory disease in dogs. To better understand the mechanism(s) responsible for the virulence of the virus, we conducted immunological, virological, clinical, and histopathological analyses in CIV-infected dogs. CIV replicated efficiently in the respiratory system of dogs and caused severe respiratory disease. Notably, the infection...
Hemorrhagic smallpox was a rare but severe manifestation of variola virus infection that resulted in nearly 100% mortality. Here we describe intravenous (IV) inoculation of cowpox virus Brighton Red strain in cynomolgus macaques (Macaca fascicularis) which resulted in disease similar in presentation to hemorrhagic smallpox in humans. IV inoculation of macaques resulted in a uniformly lethal disease...
Rhinoviruses (RVs) are picornaviruses that are causative agents of the majority of upper respiratory tract infections, or “common colds,” in humans. RVs infect both the upper and lower respiratory tract, and in addition to the common cold may also cause pneumonia, complications in patients with chronic lung diseases such as cystic fibrosis, and asthma exacerbations. Convenient animal models are not...
Simian Hemorrhagic Fever Virus (SHFV) has caused sporadic outbreaks of hemorrhagic fevers in macaques at primate research facilities. SHFV is a BSL-2 pathogen that has not been linked to human disease; as such, investigation of SHFV pathogenesis in non-human primates (NHPs) could serve as a model for hemorrhagic fever viruses such as Ebola, Marburg, and Lassa viruses. Here we describe the pathogenesis...
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