Distinct Pathways of Viral Spread in the Host Determined by Reovirus S1 Gene Segment

Tyler, Kenneth L.; McPhee, Dale A.; Fields, Bernard N.

doi:10.1126/science.3016895

Cited by 188 publications

(203 citation statements)

References 37 publications

Supporting

Mentioning

199

Contrasting

Order By: Relevance

“…Infection with various strains of the virus have been shown to cause a variety of conditions including hepatitis, lymphoma, pancreatitis, necrotizing encephalitis, and myocarditis. [23][24][25][26][27] However, the development of distal extremity necrosis has not been previously characterized in association with reovirus infection in mice.…”

Section: Discussionmentioning

confidence: 99%

Morbidity in immunosuppressed (SCID/NOD) mice treated with reovirus (Dearing 3) as an anti-cancer biotherapeutic

Loken¹,

Norman²,

Hirasawa³

et al. 2004

Cancer Biology & Therapy

View full text Add to dashboard Cite

KEY WORDSReovirus, SCID mice, cancer biotherapy, distal necrosis, vasculitis, myocarditis ACKNOWLEDGEMENTSThe authors would like to thank Calgary Laboratory Services for salary support (D.J.D.) and assistance with the histology studies. Oncolytics and Dr. Matt Coffey are gratefully acknowledged for their funding of the immunostaining costs of the project. The Patrick Lee laboratory is acknowledged for the gift of SCID mice treated with reovirus, and the anti-reovirus sera. The Don Morris laboratory is also acknowledged for the gift of mouse specimens. Research Paper Morbidity in Immunosuppressed (SCID/NOD) Mice Treated with Reovirus (Dearing 3) as an Anti-Cancer Biotherapeutic ABSTRACTSpecific viral oncolysis of cancer cells has aroused great interest as a potential anti-cancer therapy. Reovirus was proposed as an anti-cancer biotherapeutic several years ago, as it elicits virus-mediated death of human cancer cells both in vitro and in mouse model systems. A common model system for reovirus oncolysis is the NOD/ LtSz-scid/scid (SCID/NOD) immunocomprimised mouse. While human tumour xenografts are effectively killed by intra-tumour injections of reovirus, the mice often exhibit discoloration and necrosis of extremities including feet, distal leg, tail and ears several weeks after injection. This phenomenon never occurs in sham-injected mice, nor is it observed in wild type or nude mice. The pathogenesis of this "Black Foot" lesion has not yet been described, but may be of relevance for future human studies of biotherapeutics.Examination of SCID/NOD mice was performed at various time points following intratumoral injection of reovirus. Immunohistological evaluation of tissues reveals infection of cardiac myocytes and venous endothelial cells at approximately 2 days post infection. Over time, venules and veins showed a mixed inflammatory vasculitis and thrombus formation. Synchronously, the heart showed diffuse myocyte death, with dystrophic calcification. The results indicate that the "Black Foot" syndrome is likely due to venous vasculitis secondary to reovirus infection, on a background of reovirus myocarditis and heart failure. The rationale for the selective susceptibility of venous over arterial endothelium to reovirus infection is currently unknown. The results of this study may be relevant to the use of oncolytic viruses, particularly reovirus, in the anti-cancer therapy of immunosuppressed patients.

show abstract

Section: Discussionmentioning

confidence: 99%

Morbidity in immunosuppressed (SCID/NOD) mice treated with reovirus (Dearing 3) as an anti-cancer biotherapeutic

Loken¹,

Norman²,

Hirasawa³

et al. 2004

Cancer Biology & Therapy

View full text Add to dashboard Cite

show abstract

“…Investigation of viral transport in the nervous system has mainly focused on in vivo studies. It has been postulated that neurotropic viruses are transported via nerve tracts into the nervous system (Bak et al, 1977;Carbone et al, 1987;Dal Canto et al, 1986;Gillet et al, 1986;Kaluza et al, 1987;Kimberlin & Walker, 1986;Klein & DeStefano, 1983;Kucera et al, 1985;Tyler et al, 1987). However in most of these observations, the possibility that other cell types or that other mechanisms may be involved in addition to the specific neural transport has not been totally discarded.…”

Section: Introductionmentioning

confidence: 88%

The Anterograde Transport of Rabies Virus in Rat Sensory Dorsal Root Ganglia Neurons

Tsiang¹,

Lycke²,

Ceccaldi³

et al. 1989

Journal of General Virology

View full text Add to dashboard Cite

SUMMARYWe have previously described the capacity of neurites extending from cultured rat sensory dorsal root ganglia (DRG) neurons to transport rabies virus through axoplasm in the retrograde direction. Here we report the infection of cultured neurons derived from the DRG and the subsequent anterograde transport of rabies virus from the infected cell somas through the extending neurites to its release into the culture supernatant. Viral transport was monitored by titration of the virus yield in the external compartment. Both early and late transport mechanisms of rabies virions were identified. The first one occurred a few hours post-infection and was undetectable 6 h later, before the initiation of viral replication. The velocity of this first wave of infective virions was in the range of 100 to 400 mm/day. The early viral transport was probably the result of a direct translocation of infective virions from the somatic site of entry to the neuritic extensions and subsequent release into the culture medium without replication in the cellular perikaryon. The second virus transport peak was detected 48 h post-infection. In this case, the virions detected in the neuritic compartment were presumably the progeny of the inoculated virus which had replicated in the perikaryon before the viral transport occurs. Using a four-compartment culture device we were able to demonstrate, simultaneously, retrograde and anterograde transport of the virus. The presence of antirabies serum in contact with the exposed neurites did not inhibit either the retrograde or the anterograde transport mechanisms. The viral release from the neuritic extensions after the fast anterograde transport was evaluated to be in the range of 150 to 300 infectious virions per bundle of neurites per day.

show abstract

“…Previous studies have shown that neurotropic viruses can initiate infection in the periphery and can move through peripheral neurons to reach the central nervous system (Card et al, 1991;Ohka et al, 1998;Samuel et al, 2007;Tyler et al, 1986). Therefore, we hypothesized that mice with neurotropic disease may have higher viral titres in peripheral neurons and brain.…”

Section: Yfv-17d Titres In Ifnar "/" Micementioning

confidence: 97%

Spectrum of disease outcomes in mice infected with YFV-17D

Erickson

Pfeiffer

2015

Journal of General Virology

View full text Add to dashboard Cite

Distinct Pathways of Viral Spread in the Host Determined by Reovirus S1 Gene Segment

Cited by 188 publications

References 37 publications

Morbidity in immunosuppressed (SCID/NOD) mice treated with reovirus (Dearing 3) as an anti-cancer biotherapeutic

Morbidity in immunosuppressed (SCID/NOD) mice treated with reovirus (Dearing 3) as an anti-cancer biotherapeutic

The Anterograde Transport of Rabies Virus in Rat Sensory Dorsal Root Ganglia Neurons

Spectrum of disease outcomes in mice infected with YFV-17D

Contact Info

Product

Resources

About