scholarly journals Sequencing of Historical Isolates, K-mer Mining and High Serological Cross-Reactivity with Ross River Virus Argue against the Presence of Getah Virus in Australia

Pathogens ◽  
2020 ◽  
Vol 9 (10) ◽  
pp. 848
Author(s):  
Daniel J. Rawle ◽  
Wilson Nguyen ◽  
Troy Dumenil ◽  
Rhys Parry ◽  
David Warrilow ◽  
...  
Keyword(s):  
Mouse Model ◽  
Sequence Data ◽  
Wild Type Mouse ◽  
Cross Reactivity ◽  
Cross Protection ◽  
Ross River Virus ◽  
Wild Type ◽  
Serological Relationship ◽  
Sequence Read Archive ◽  
Getah Virus

Getah virus (GETV) is a mosquito-transmitted alphavirus primarily associated with disease in horses and pigs in Asia. GETV was also reported to have been isolated from mosquitoes in Australia in 1961; however, retrieval and sequencing of the original isolates (N544 and N554), illustrated that these viruses were virtually identical to the 1955 GETVMM2021 isolate from Malaysia. K-mer mining of the >40,000 terabases of sequence data in the Sequence Read Archive followed by BLASTn confirmation identified multiple GETV sequences in biosamples from Asia (often as contaminants), but not in biosamples from Australia. In contrast, sequence reads aligning to the Australian Ross River virus (RRV) were readily identified in Australian biosamples. To explore the serological relationship between GETV and other alphaviruses, an adult wild-type mouse model of GETV was established. High levels of cross-reactivity and cross-protection were evident for convalescent sera from mice infected with GETV or RRV, highlighting the difficulties associated with the interpretation of early serosurveys reporting GETV antibodies in Australian cattle and pigs. The evidence that GETV circulates in Australia is thus not compelling.

scholarly journals A Host-Restricted Self-Attenuated Influenza Virus Provides Broad Pan-Influenza A Protection in a Mouse Model

2021 ◽  
Vol 12 ◽  
Author(s):  
Minjin Kim ◽  
Yucheol Cheong ◽  
Jinhee Lee ◽  
Jongkwan Lim ◽  
Sanguine Byun ◽  
...  
Keyword(s):  
Influenza Virus ◽  
Mouse Model ◽  
Neutralizing Antibodies ◽  
Influenza A ◽  
Protective Efficacy ◽  
Influenza Viruses ◽  
Cross Protection ◽  
Infection Model ◽  
Wild Type ◽  
Group 1

Influenza virus infections can cause a broad range of symptoms, form mild respiratory problems to severe and fatal complications. While influenza virus poses a global health threat, the frequent antigenic change often significantly compromises the protective efficacy of seasonal vaccines, further increasing the vulnerability to viral infection. Therefore, it is in great need to employ strategies for the development of universal influenza vaccines (UIVs) which can elicit broad protection against diverse influenza viruses. Using a mouse infection model, we examined the breadth of protection of the caspase-triggered live attenuated influenza vaccine (ctLAIV), which was self-attenuated by the host caspase-dependent cleavage of internal viral proteins. A single vaccination in mice induced a broad reactive antibody response against four different influenza viruses, H1 and rH5 (HA group 1) and H3 and rH7 subtypes (HA group 2). Notably, despite the lack of detectable neutralizing antibodies, the vaccination provided heterosubtypic protection against the lethal challenge with the viruses. Sterile protection was confirmed by the complete absence of viral titers in the lungs and nasal turbinates after the challenge. Antibody-dependent cellular cytotoxicity (ADCC) activities of non-neutralizing antibodies contributed to cross-protection. The cross-protection remained robust even after in vivo depletion of T cells or NK cells, reflecting the strength and breadth of the antibody-dependent effector function. The robust mucosal secretion of sIgA reflects an additional level of cross-protection. Our data show that the host-restricted designer vaccine serves an option for developing a UIV, providing pan-influenza A protection against both group 1 and 2 influenza viruses. The present results of potency and breadth of protection from wild type and reassortant viruses addressed in the mouse model by single immunization merits further confirmation and validation, preferably in clinically relevant ferret models with wild type challenges.

scholarly journals Chikungunya Virus Arthritis in Adult Wild-Type Mice

2010 ◽  
Vol 84 (16) ◽  
pp. 8021-8032 ◽  
Author(s):  
Joy Gardner ◽  
Itaru Anraku ◽  
Thuy T. Le ◽  
Thibaut Larcher ◽  
Lee Major ◽  
...  
Keyword(s):  
Mouse Model ◽  
Rheumatic Disease ◽  
Chikungunya Virus ◽  
Virus Disease ◽  
Ross River Virus ◽  
Reunion Island ◽  
Wild Type ◽  
Primary Mouse ◽  
Réunion Island ◽  
Asian Isolate

ABSTRACT Chikungunya virus is a mosquito-borne arthrogenic alphavirus that has recently reemerged to produce the largest epidemic ever documented for this virus. Here we describe a new adult wild-type mouse model of chikungunya virus arthritis, which recapitulates the self-limiting arthritis, tenosynovitis, and myositis seen in humans. Rheumatic disease was associated with a prolific infiltrate of monocytes, macrophages, and NK cells and the production of monocyte chemoattractant protein 1 (MCP-1), tumor necrosis factor alpha (TNF-α), and gamma interferon (IFN-γ). Infection with a virus isolate from the recent Reunion Island epidemic induced significantly more mononuclear infiltrates, proinflammatory mediators, and foot swelling than did an Asian isolate from the 1960s. Primary mouse macrophages were shown to be productively infected with chikungunya virus; however, the depletion of macrophages ameliorated rheumatic disease and prolonged the viremia. Only 1 μg of an unadjuvanted, inactivated, whole-virus vaccine derived from the Asian isolate completely protected against viremia and arthritis induced by the Reunion Island isolate, illustrating that protection is not strain specific and that low levels of immunity are sufficient to mediate protection. IFN-α treatment was able to prevent arthritis only if given before infection, suggesting that IFN-α is not a viable therapy. Prior infection with Ross River virus, a related arthrogenic alphavirus, and anti-Ross River virus antibodies protected mice against chikungunya virus disease, suggesting that individuals previously exposed to Ross River virus should be protected from chikungunya virus disease. This new mouse model of chikungunya virus disease thus provides insights into pathogenesis and a simple and convenient system to test potential new interventions.

scholarly journals Transplantation of wild-type mouse hematopoietic stem and progenitor cells ameliorates deficits in a mouse model of Friedreich’s ataxia

2017 ◽  
Vol 9 (413) ◽  
pp. eaaj2347 ◽  
Author(s):  
Celine J. Rocca ◽  
Spencer M. Goodman ◽  
Jennifer N. Dulin ◽  
Joseph H. Haquang ◽  
Ilya Gertsman ◽  
...  
Keyword(s):  
Mouse Model ◽  
Progenitor Cells ◽  
Wild Type Mouse ◽  
Friedreich’S Ataxia ◽  
Friedreich's Ataxia ◽  
Wild Type ◽  
Hematopoietic Stem ◽  
Stem And Progenitor Cells

Characterizing the BMP pathway in a wild type mouse model of distraction osteogenesis

Bone ◽  
2008 ◽  
Vol 42 (6) ◽  
pp. 1144-1153 ◽  
Author(s):  
Tasima Haque ◽  
Fares Hamade ◽  
Norine Alam ◽  
Maria Kotsiopriftis ◽  
Dominique Lauzier ◽  
...  
Keyword(s):  
Mouse Model ◽  
Distraction Osteogenesis ◽  
Wild Type Mouse ◽  
Wild Type ◽  
Bmp Pathway

Intravesical anti-PD-1 immune checkpoint inhibition in urothelial bladder cancer in a mouse model.

2020 ◽  
Vol 38 (6_suppl) ◽  
pp. 537-537
Author(s):  
Anne Rajkumar ◽  
Jian Wang ◽  
Kevin E. Neuzil ◽  
Austin Noah Kirschner ◽  
Sam S. Chang
Keyword(s):  
Bladder Cancer ◽  
Mouse Model ◽  
Immune Checkpoint ◽  
Intraperitoneal Administration ◽  
Wild Type Mouse ◽  
Wild Type ◽  
Urothelial Bladder Cancer ◽  
Intravesical Administration ◽  
Antibody Treatment ◽  
Urothelial Bladder

537 Background: Non-muscle-invasive bladder cancer is treated by resection within the bladder and bladder instillment with BCG or chemotherapy, but the majority of intermediate- and high-risk cases subsequently recur. Systemic administration of anti-PD-1 immune checkpoint inhibitors (anti-PD-1) are approved treatments for metastatic urothelial bladder cancer. We hypothesized that intravesical instillment with an anti-PD-1 inhibitor would treat localized bladder cancer. Methods: We investigated a syngeneic wild-type mouse model of orthotopic urothelial bladder cancer. We instilled MBT2 cells into wild-type C3H mice to compare treatments, which included weekly intravesical administration of chemotherapy and anti-PD-1 antibody alongside intraperitoneal administration of anti-PD1 antibody. Results: Anti-PD-1 antibody administered by bladder instillment (intravesical route) successfully treats the disease, similarly to anti-PD-1 by systemic route. Anti-PD-1 antibody by either route provides significant survival advantage over isotype control antibody given by bladder instillment. Treatment by immune checkpoint inhibitor increases CD8+ cell infiltration in tumors, particularly when administered intravesically. In addition, antibody treatment avoids toxicity observed for intravesical chemotherapy. Mice who cleared their tumors after initial treatment were rechallenged with tumor engraftment 3-9 months later without any additional treatment, showing initial-anti-PD-1 treated mice did not grow tumors but initial mitomycin-treated mice did grow tumors. Conclusions: Intravesical administration of anti-PD-1 is a promising avenue for treatment of localized bladder cancer, with comparable anti-tumor activity compared to systemic anti-PD-1 in this mouse model.

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