Human coronavirus OC43 infection induces chronic encephalitis leading to disabilities in BALB/C mice

Jacomy, Hélène; Fragoso, Gabriela; Almazán, Guillermina; Mushynski, Walter E.; Talbot, Pierre J.

doi:10.1016/j.virol.2006.01.049

Cited by 177 publications

(211 citation statements)

References 66 publications

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“…HCoV-OC43, a respiratory CoV, could be a powerful tool for gaining new insights into the neurological manifestations and neurotropic mechanisms of other respiratory viruses. In the present study, our data demonstrated that rOC43-ns2DelRluc levels reflected HCoV-OC43-WT replication in the brain and its spread to the spinal cord of living mice, with bioluminescence intensity directly correlating with viral loads as measured by IFA and western blot and consistent with previous studies (Dubé et al, 2018;Jacomy et al, 2006).…”

Section: Discussionsupporting

confidence: 92%

“…CoVs, which cause respiratory diseases, have also been associated with neurological complications (Arabi et al, 2015;Arbour et al, 2000;Burks et al, 1980;Hung et al, 2003;Netland et al, 2008), with HCoV-OC43 even causing fatal encephalitis (Jacomy et al, 2006;Jacomy and Talbot, 2003;Morfopoulou et al, 2016); however, the mechanisms responsible for their dissemination and penetration in the host CNS remain unclear. Therefore, easily observable, living animal models are required to identify the mechanisms of HCoV infection in the CNS and enable the development of antiviral drugs for treating and preventing CoV infection and their associated severe CNS pathologies.…”

Section: Discussionmentioning

confidence: 99%

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Non-invasive bioluminescence imaging of HCoV-OC43 infection and therapy in the central nervous system of live mice

et al. 2020

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Human coronaviruses (HCoVs) are important pathogens that cause upper respiratory tract infections and have neuroinvasive abilities; however, little is known about the dynamic infection process of CoVs in vivo, and there are currently no specific antiviral drugs to prevent or treat HCoV infection. Here, we verified the replication ability and pathogenicity of a reporter HCoV-OC43 strain expressing Renilla luciferase (Rluc; rOC43-ns2DelRluc) in mice with different genetic backgrounds (C57BL/6 and BALB/c). Additionally, we monitored the spatial and temporal progression of HCoV-OC43 through the central nervous system (CNS) of live BALB/c mice after intranasal or intracerebral inoculation with rOC43-ns2DelRluc. We found that rOC43-ns2DelRluc was fatal to suckling mice after intranasal inoculation, and that viral titers and Rluc expression were detected in the brains and spinal cords of mice infected with rOC43-ns2DelRluc. Moreover, viral replication was initially observed in the brain by non-invasive bioluminescence imaging before the infection spread to the spinal cord of BALB/c mice, consistent with its tropism in the CNS. Furthermore, the Rluc readout correlated with the HCoV replication ability and protein expression, which allowed quantification of antiviral activity in live mice. Additionally, we validated that chloroquine strongly inhibited rOC43-ns2DelRluc replication in vivo. These results provide new insights into the temporal and spatial dissemination of HCoV-OC43 in the CNS, and our methods provide an extremely sensitive platform for evaluating the efficacy of antiviral therapies to treat neuroinvasive HCoVs in live mice.

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Section: Discussionsupporting

confidence: 92%

Section: Discussionmentioning

confidence: 99%

Non-invasive bioluminescence imaging of HCoV-OC43 infection and therapy in the central nervous system of live mice

et al. 2020

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“…However, there is also direct evidence for involvement in enteric (e.g. strain HECoV 4408) (Zhang et al, 1994;Zhu et al, 2006) and suggestive evidence for involvement in neurological disease (Clarke et al, 1979;Flewett et al, 1987;Foley and Leutenegger, 2001;Gerna et al, 1985Gerna et al, , 1984Han et al, 2006;Jacomy et al, 2006;Luby et al, 1999;Resta et al, 1985;Saif, 2004;Schnagl et al, 1990Schnagl et al, , 1986Sitbon, 1985;Vabret et al, 2006;Zhu et al, 2006). HCoV are frequent causes of the common cold; usually a self-limiting upper respiratory tract (URT) illness (Heikkinen and Jarvinen, 2003).…”

Section: Introductionmentioning

confidence: 99%

Broadly targeted multiprobe QPCR for detection of coronaviruses: Coronavirus is common among mallard ducks (Anas platyrhynchos)

Muradrasoli

Mohamed

Hornyák

et al. 2009

Journal of Virological Methods

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Coronaviruses (CoVs) can cause trivial or fatal disease in humans and in animals. Detection methods for a wide range of CoVs are needed, to understand viral evolution, host range, transmission and maintenance in reservoirs. A new concept, "Multiprobe QPCR", which uses a balanced mixture of competing discrete non- or moderately degenerated nuclease degradable (TaqMan) probes was employed. It provides a broadly targeted and rational single tube real-time reverse transcription PCR ("NQPCR") for the generic detection and discovery of CoV. Degenerate primers, previously published, and the new probes, were from a conserved stretch of open reading frame 1b, encoding the replicase. This multiprobe design reduced the degree of probe degeneration, which otherwise decreases the sensitivity, and allowed a preliminary classification of the amplified sequence directly from the QPCR trace. The split probe strategy allowed detection of down to 10 viral nucleic acid equivalents of CoV from all known CoV groups. Evaluation was with reference CoV strains, synthetic targets, human respiratory samples and avian fecal samples. Infectious-Bronchitis-Virus (IBV)-related variants were found in 7 of 35 sample pools, from 100 wild mallards (Anas platyrhynchos). Ducks may spread and harbour CoVs. NQPCR can detect a wide range of CoVs, as illustrated for humans and ducks.

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“…Virus was propagated and titrated on Vero cells as described previously (Lymberopoulos & Pearson, 2007). Primary embryonic neurons were harvested from E16-18 CD-1 mice (Jacomy et al, 2006). LA-N-5 cells were maintained and differentiated with RA (Hill & Robertson, 1998).…”

Section: Methodsmentioning

confidence: 99%

Mutation of UL24 impedes the dissemination of acute herpes simplex virus 1 infection from the cornea to neurons of trigeminal ganglia

Rochette

Bourget

Sanabria-Solano

et al. 2015

Journal of General Virology

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Herpes simplex virus 1 (human herpesvirus 1) initially infects epithelial cells of the mucosa and then goes on to infect sensory neurons leading ultimately to a latent infection in trigeminal ganglia (TG). UL24 is a core herpesvirus gene that has been identified as a determinant of pathogenesis in several Alphaherpesvirinae, although the underlying mechanisms are unknown. In a mouse model of ocular infection, a UL24-deficient virus exhibited a reduction in viral titres in tear films of 1 log 10 , whilst titres in TG are often below the level of detection. Moreover, the efficiency of reactivation from latency was also severely reduced. Herein, we investigated how UL24 contributed to acute infection of TG. Our results comparing the impact of UL24 on viral titres in eye tissue versus in tear films did not reveal a general defect in virus release from the cornea. We also found that the impairment of replication seen in mouse primary embryonic neurons with a UL24-deficient virus was not more severe than that observed in an epithelial cell line. Rather, in situ histological analyses revealed that infection with a UL24-deficient virus led to a significant reduction in the number of acutely infected neurons at 3 days post-infection (p.i.). Moreover, there was a significant reduction in the number of neurons positive for viral DNA at 2 days p.i. for the UL24-deficient virus as compared with that observed for WT or a rescue virus. Our results supported a model whereby UL24 functions in the dissemination of acute infection from the cornea to neurons in TG.

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Human coronavirus OC43 infection induces chronic encephalitis leading to disabilities in BALB/C mice

Cited by 177 publications

References 66 publications

Non-invasive bioluminescence imaging of HCoV-OC43 infection and therapy in the central nervous system of live mice

Non-invasive bioluminescence imaging of HCoV-OC43 infection and therapy in the central nervous system of live mice

Broadly targeted multiprobe QPCR for detection of coronaviruses: Coronavirus is common among mallard ducks (Anas platyrhynchos)

Mutation of UL24 impedes the dissemination of acute herpes simplex virus 1 infection from the cornea to neurons of trigeminal ganglia

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