Monitoring of emerging myxoma virus epidemics in Iberian hares ( Lepus granatensis ) in Spain, 2018–2020

2020 ◽  
Author(s):  
Ignacio García‐Bocanegra ◽  
Leonor Camacho‐Sillero ◽  
Javier Caballero‐Gómez ◽  
Montserrat Agüero ◽  
Félix Gómez‐Guillamón ◽  
...  
Keyword(s):  
Myxoma Virus ◽  
Lepus Granatensis

scholarly journals Genetic characterization of a recombinant myxoma virus leap into the Iberian hare (Lepus granatensis)

2019 ◽  
Author(s):  
Ana Águeda-Pinto ◽  
Ana Lemos de Matos ◽  
Mário Abrantes ◽  
Simona Kraberger ◽  
Maria A. Risalde ◽  
...  
Keyword(s):  
Myxoma Virus ◽  
Open Reading Frames ◽  
Lepus Europaeus ◽  
European Rabbit ◽  
New Host ◽  
Tissue Samples ◽  
Lepus Granatensis ◽  
Domestic Rabbits ◽  
Iberian Hare

AbstractMyxomatosis is a lethal disease of wild European and domestic rabbits (Oryctolagus cuniculus) caused by a Myxoma virus (MYXV) infection, a leporipoxvirus that is found naturally in someSylvilagusrabbit species in South America and California. The introduction of MYXV in the early 1950s into feral European rabbit populations in Australia and Europe demonstrate the best documented field example of host-virus coevolution following a cross-species transmission. Recently, a new cross-species jump of MYXV has been suggested in both Great Britain and Spain, where European brown hares (Lepus europaeus) and Iberian hares (Lepus granatensis) were found dead with lesions consistent with those observed in myxomatosis. To investigate the possibility of a new cross-species transmission event by MYXV, tissue samples collected from a wild Iberian hare found dead in Spain (Toledo region) were analyzed and deep sequenced. Our results report a new MYXV strain (MYXV Toledo) in the tissues of this species. The genome of this new strain encodes three disrupted genes (M009L,M036LandM152R) and a novel 2.8 KB recombinant region that resulted from an insertion of four novel poxviral genes towards the 5’ end of its genome. From the open reading frames inserted into the MYXV Toledo strain, a new orthologue of a poxvirus host range gene family member was identified which is related to the MYXV geneM064R. Overall, we confirmed the identity of a new MYXV strain in Iberian hares that we hypothesize was able to more effectively counteract the host defenses in hares and start an infectious process in this new host.

First cases of myxomatosis in Iberian hares (Lepus granatensis) in Portugal

2020 ◽  
Vol 8 (2) ◽  
pp. e001044 ◽  
Author(s):  
Carina Luísa Carvalho ◽  
Fábio Alexandre Abade dos Santos ◽  
Madelena Monteiro ◽  
Paulo Carvalho ◽  
Paula Mendonça ◽  
...  
Keyword(s):  
Body Condition ◽  
Myxoma Virus ◽  
Common Origin ◽  
Lepus Granatensis ◽  
Short Course ◽  
Good Body Condition ◽  
Myxoid Matrix ◽  
Gross Lesions ◽  
Perineal Region ◽  
Iberian Hare

Myxomatosis was detected in Iberian hares (Lepus granatensis) in Portugal, October 2018, following its emergence in Spain 3 months earlier. Here, we describe the epidemiological, molecular and anatomo-histopathological data of the first two cases. Myxoma virus DNA was detected in the eyelids, nose and perineal region in both hares. It was also detected in the lungs of hare 1 and in the spleen and liver of hare 2. The genomic insertion identified in strains from Spain was confirmed in both strains suggesting a common origin for the Iberian viruses. Gross lesions in hare 1 included palpebral oedema and conjunctival mucopurulent discharge, common in both forms of the disease in rabbits. Hare 2 presented eyelid thickening with small diffuse nodules. Histopathology of the eyelids showed extracellular myxoid matrix in hare 1 and purulent dermatitis in hare 2. Both animals exhibited good body condition, suggesting a short course of the disease and higher virulence of the virus towards the Iberian hare.

scholarly journals Genetic Characterization of a Recombinant Myxoma Virus in the Iberian Hare (Lepus granatensis)

Viruses ◽  
2019 ◽  
Vol 11 (6) ◽  
pp. 530 ◽  
Author(s):  
Ana Águeda-Pinto ◽  
Ana Lemos de Matos ◽  
Mário Abrantes ◽  
Simona Kraberger ◽  
Maria A. Risalde ◽  
...  
Keyword(s):  
Myxoma Virus ◽  
Open Reading Frames ◽  
Lepus Europaeus ◽  
European Rabbit ◽  
New Host ◽  
Tissue Samples ◽  
Lepus Granatensis ◽  
Domestic Rabbits ◽  
Iberian Hare

Myxomatosis is a lethal disease in wild European and domestic rabbits (Oryctolagus cuniculus), which is caused by a Myxoma virus (MYXV) infection—a leporipoxvirus that is found naturally in some Sylvilagus rabbit species in South America and California. The introduction of MYXV into feral European rabbit populations of Australia and Europe, in the early 1950s, demonstrated the best-documented field example of host–virus coevolution, following a cross-species transmission. Recently, a new cross-species jump of MYXV has been suggested in both Great Britain and Spain, where European brown hares (Lepus europaeus) and Iberian hares (Lepus granatensis) were found dead with lesions consistent with those observed in myxomatosis. To investigate the possibility of a new cross-species transmission event by MYXV, tissue samples collected from a wild Iberian hare found dead in Spain (Toledo region) were analyzed and deep sequenced. Our results reported a new MYXV isolate (MYXV Toledo) in the tissues of this species. The genome of this new virus was found to encode three disruptive genes (M009L, M036L, and M152R) and a novel ~2.8 kb recombinant region, which resulted from an insertion of four novel poxviral genes towards the 3’ end of the negative strand of its genome. From the open reading frames inserted into the MYXV Toledo virus, a new orthologue of a poxvirus host range gene family member was identified, which was related to the MYXV gene M064R. Overall, we confirmed the identity of a new MYXV isolate in Iberian hares, which, we hypothesized, was able to more effectively counteract the host defenses in hares and start an infectious process in this new host.

scholarly journals The differential transmissibility of myxoma virus strains of differing virulence grades by the rabbit flea Spilopsyllus cuniculi (Dale)

1975 ◽  
Vol 75 (2) ◽  
pp. 237-247 ◽  
Author(s):  
A. R. Mead-Briggs ◽  
J. A. Vaughan
Keyword(s):  
Host Resistance ◽  
Oryctolagus Cuniculus ◽  
Selective Advantage ◽  
Myxoma Virus ◽  
Laboratory Studies ◽  
Natural Conditions ◽  
Male And Female ◽  
The Mean ◽  
Virus Strains ◽  
Sampling Times

SUMMARYLaboratory studies showed that few rabbit fleas (Spilopsyllus cuniculi (Dale)) transmitted myxomatosis after removal from wild rabbits (Oryctolagus cuniculus (L)) that had been infected for fewer than 10–12 days, irrespective of the virulence of the myxoma virus strain involved. Rabbits infected with fully virulent (Grade I) strains died within 10–15 days and few fleas from these hosts became infective; averaging all the samples taken, 12% of the fleas were infective. Also, few fleas acquired infectivity on individual rabbits which recovered from infection with attenuated strains; the mean was 8% infective. Rabbits which died between 17 and 44 days after infection had higher proportions of infective fleas at all sampling times; the mean was 42% infective. Male and female fleas transmitted virus with equal efficiency.For rabbits infected with any of the attenuated virus strains the mean percentage of infective fleas was inversely related to the survival time of the host. Rabbits infected with moderately attenuated strains (Grades IIIA and IIIB) had, on average, the highest proportion of infective fleas; hence such strains have a selective advantage and have become predominant under natural conditions in Britain. The changes that might occur if there is an increase in host resistance to myxomatosis are discussed.

Myxoma virus and malignant rabbit fibroma virus encode a serpin-like protein important for virus virulence

Virology ◽  
1990 ◽  
Vol 179 (2) ◽  
pp. 618-631 ◽  
Author(s):  
C. Upton ◽  
J.L. Macen ◽  
D.S. Wishart ◽  
G. McFadden
Keyword(s):  
Myxoma Virus

Abstract 1921: Armed oncolytic myxoma virus demonstrates efficacy in syngeneic tumor models alone and in combination with immune checkpoint inhibitors

2021 ◽  
Author(s):  
Lina S. Franco ◽  
Joseph Mamola ◽  
Wazir Abdullahi ◽  
Ana de Matos ◽  
Mario Abrantes ◽  
...  
Keyword(s):  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Myxoma Virus ◽  
Tumor Models ◽  
Syngeneic Tumor

scholarly journals Myxoma Virus Optimizes Cisplatin for the Treatment of Ovarian Cancer In Vitro and in a Syngeneic Murine Dissemination Model

2017 ◽  
Vol 6 ◽  
pp. 90-99 ◽  
Author(s):  
Bernice Nounamo ◽  
Jason Liem ◽  
Martin Cannon ◽  
Jia Liu
Keyword(s):  
Ovarian Cancer ◽  
Myxoma Virus

Myxoma Virus Expresses a TNF Receptor Homolog with two Distinct Functions

2000 ◽  
pp. 97-109
Author(s):  
Xiaoming Xu ◽  
Piers Nash ◽  
Grant McFadden
Keyword(s):  
Myxoma Virus ◽  
Tnf Receptor

scholarly journals 947 Recombinant myxoma virus MC509-N1 demonstrates antitumor efficacy as monotherapy and in combination with immune checkpoint inhibitors

2021 ◽  
Vol 9 (Suppl 3) ◽  
pp. A996-A996
Author(s):  
Enkhtaivan Gansukh ◽  
Tommy Alain ◽  
Tae-Geuk Kim ◽  
Ye-Na Namgung ◽  
Ka-Yeon Son ◽  
...  
Keyword(s):  
Flow Cytometry ◽  
Tumor Microenvironment ◽  
Tumor Growth ◽  
Immune Checkpoint ◽  
Myxoma Virus ◽  
Wild Type ◽  
Anticancer Efficacy ◽  
Immune Profile ◽  
Immune State ◽  
Inhibition Of Tumor Growth

BackgroundThere are several obstacles to effective cancer immunotherapy including the heterogenic immune profile and the state of the tumor microenvironment. Oncolytic virotherapy provides an opportunity to overcome some of these limitations through high viral replication and the expression of therapeutic transgenes (TGs) within the tumor tissue. Myxoma virus (MYXV) belongs to the family of Poxviridae and represents a potent oncolytic virus and a safe platform as this virus is non-pathogenic in any hosts apart from lagomorphs. Importantly, MYXV has a high capacity of encoding for multiple TG payloads. Here we engineered MC509-N1, a novel double-encoding transgenes (TG1 and TG2) oncolytic MYXV designed for intravenous (IV) injection. The therapeutic TG1 acts to modify and remodel the immune state of the tumor microenvironment, and TG2 allows for prolonged self-evasion from the host immune defense.MethodsTransgenes expression upon infection was detected by ELISA and by flow cytometry. To determine anticancer efficacy, syngeneic B16F10 melanoma or MC38 colorectal cancer-bearing C57BL/6 mice were injected with MC509-N1 intratumorally or IV with or without immune checkpoint inhibitor (ICI). Tumor growth and survival was monitored after treatment and the immune profile within the tumor microenvironment was analyzed by flow cytometry. Mice cured of their tumors from the original treatment were rechallenged with primary tumor cells to examine anticancer immunity.ResultsCells upon infection with MC509-N1 were found to express both transgenes at high levels and stimulate downstream mechanisms. Importantly, the engineering of both transgenes did not affect MC509-N1 infectivity and productivity as compared to wild-type MYXV. Intratumoral injections of MC509-N1 effectively suppressed tumor growth and improved overall survival of both syngeneic cancer models. Furthermore, MC509-N1 therapy effectively modulated the immune profile within the tumor microenvironment, especially the ratio between tumor infiltrated CD8+ cytotoxic T cells and CD4+FoxP3+ T regulatory cells. In addition, IV injections of MC509-N1 showed improved inhibition of tumor growth compared to wild type MYXV. The combination therapy of MC509-N1 with the ICI anti-PD-L1 further promoted inhibition of tumor growth as demonstrated by higher rate of complete regression and improved survival rate. Furthermore, rechallenge experiments revealed that this combination regimen established specific anticancer immune memory and protected from cancer recurrence.ConclusionsOur results demonstrate that the novel engineered MC509-N1 exhibits potent anticancer efficacy, adequately modulates the immune state of the tumor microenvironment, and acts synergistically to eliminate cancer in combination with ICI.

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