Coronaviruses infect many species of animals including humans, causing acute and chronic diseases. This review focuses primarily on the pathogenesis of murine coronavirus mouse hepatitis virus (MHV) and severe acute respiratory coronavirus (SARS-CoV). MHV is a collection of strains, which provide models systems for the study of viral tropism and pathogenesis in several organs systems, including the central nervous system, the liver, and the lung, and has been cited as providing one of the few animal models for the study of chronic demyelinating diseases such as multiple sclerosis. SARS-CoV emerged in the human population in China in 2002, causing a worldwide epidemic with severe morbidity and high mortality rates, particularly in older individuals. We review the pathogenesis of both viruses and the several reverse genetics systems that made much of these studies possible. We also review the functions of coronavirus proteins, structural, enzymatic, and accessory, with an emphasis on roles in pathogenesis. Structural proteins in addition to their roles in virion structure and morphogenesis also contribute significantly to viral spread in vivo and in antagonizing host cell responses. Nonstructural proteins include the small accessory proteins that are not at all conserved between MHV and SARS-CoV and the 16 conserved proteins encoded in the replicase locus, many of which have enzymatic activities in RNA metabolism or protein processing in addition to functions in antagonizing host response.
"Moreover, SARS-CoV S1 protein, but not its counterpart in HCoV-HKU1, was required and sufficient for UPR activation (Figure 6). Cleavability of surface proteins by host proteases is an important virulence determinant in coronaviruses and other viruses such as influenza [1,14,37]. In this connection, it will not be too surprising if the inability of TMPRSS2 to cleave HCoV-HKU1 might affect pathogenesis. "
[Show abstract][Hide abstract] ABSTRACT: Whereas severe acute respiratory syndrome (SARS) coronavirus (SARS-CoV) is associated with severe disease, human coronavirus HKU1 (HCoV-HKU1) commonly circulates in the human populations causing generally milder illness. Spike (S) protein of SARS-CoV activates the unfolded protein response (UPR). It is not understood whether HCoV-HKU1 S protein has similar activity. In addition, the UPR-activating domain in SARS-CoV S protein remains to be identified.
In this study we compared S proteins of SARS-CoV and HCoV-HKU1 for their ability to activate the UPR. Both S proteins were found in the endoplasmic reticulum. Transmembrane serine protease TMPRSS2 catalyzed the cleavage of SARS-CoV S protein, but not the counterpart in HCoV-HKU1. Both S proteins showed a similar pattern of UPR-activating activity. Through PERK kinase they activated the transcription of UPR effector genes such as Grp78, Grp94 and CHOP. N-linked glycosylation was not required for the activation of the UPR by S proteins. S1 subunit of SARS-CoV but not its counterpart in HCoV-HKU1 was capable of activating the UPR. A central region (amino acids 201--400) of SARS-CoV S1 was required for this activity.
SARS-CoV and HCoV-HKU1 S proteins use distinct UPR-activating domains to exert the same modulatory effects on UPR signaling.
Cell and Bioscience 01/2014; 4(1):3. DOI:10.1186/2045-3701-4-3 · 3.63 Impact Factor
"This is the case, in particular, for members of the Flaviviridae family such as Hepatitis C virus (HCV), a widely spread human virus which causes a chronic infection of the liver which can lead to cirrhosis and hepatocellular carcinoma , or the arthropod-transmitted viruses, Dengue virus (DENV), West Nile Encephalitis virus (WNV) or Japanese Encephalitis virus (JEV), which can cause severe hemorrhagic or neurological syndromes in man . Members of the Coronaviridae and Arteriviridae families such as the Severe Acute Respiratory Syndrome coronavirus (SARS-CoV), the avian Infectious Bronchitis virus (IBV) and the Porcine Reproductive and Respiratory Syndrome virus (PPRSV) are also considered major pathogens causing severe respiratory diseases in man and animals . Finally, it is of particular interest to also cite the interactions reported for two members of the "
[Show abstract][Hide abstract] ABSTRACT: Viruses are small obligatory parasites and as a consequence, they have developed sophisticated strategies to exploit the host cell's functions to create an environment that favours their own replication. A common feature of most- if not all- families of human and non-human viruses concerns their interaction with the nucleolus. The nucleolus is a multifunctional nuclear domain, which, in addition to its well-known role in ribosome biogenesis, plays several crucial other functions. Viral infection induces important nucleolar alterations. Indeed, during viral infection numerous viral components localize in nucleoli, while various host nucleolar proteins are redistributed in other cell compartments or are modified, and non-nucleolar cellular proteins reach the nucleolus. This review highlights the interactions reported between the nucleolus and some human or animal viral families able to establish a latent or productive infection, selected on the basis of their known interactions with the nucleolus and the nucleolar activities, and their links with virus replication and/or pathogenesis. This article is part of a Special Issue entitled: Role of the Nucleolus in Human Disease.
"JHMV induces clinical symptoms associated with encephalitis which transitions to predominantly hind limb paralysis. Severity of clinical symptoms reflects both viral load and the antiviral immune response (Bergmann et al., 2006; Kapil et al., 2009; Weiss and Leibowitz, 2011). Anti-CD25 treatment did not alter disease onset, severity or the progression of clinical symptoms (Fig. 3A). "
[Show abstract][Hide abstract] ABSTRACT: The influence of CD25(+)CD4(+) regulatory T cells (Treg) on acute and chronic viral infection of the central nervous system (CNS) was examined using a glial tropic murine coronavirus. Treg in the CNS were highest during initial T cell mediated virus control, decreased and then remained relatively stable during persistence. Anti-CD25 treatment did not affect CNS recruitment of inflammatory cells. Viral control was initially delayed; however, neither the kinetics of viral control nor viral persistence were affected. By contrast, the absence of Treg during the acute phase resulted in increased demyelination during viral persistence. These data suggest that CNS inflammation, progression of viral control and viral persistence are relatively independent of CD25(+)CD4(+) Treg. However, their absence during acute infection alters the ability of the host to limit tissue damage.
Jayshree Samanta, Ethan M Grund, Hernandez M Silva, Juan J Lafaille, Gord Fishell, James L Salzer
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