scholarly journals The rabbit papillomavirus model: a valuable tool to study viral–host interactions

2019 ◽  
Vol 374 (1773) ◽  
pp. 20180294 ◽  
Author(s):  
Nancy M. Cladel ◽  
Xuwen Peng ◽  
Neil Christensen ◽  
Jiafen Hu
Keyword(s):  
Viral Infections ◽  
Vaccine Development ◽  
Therapeutic Vaccine ◽  
Rabbit Model ◽  
Preclinical Model ◽  
Sylvilagus Floridanus ◽  
Host Interactions ◽  
Cottontail Rabbit ◽  
Transgenic Rabbits ◽  
Viral Host Interactions

Cottontail rabbit papillomavirus (CRPV) was the first DNA virus shown to be tumorigenic. The virus has since been renamed and is officially known as Sylvilagus floridanus papillomavirus 1 (SfPV1). Since its inception as a surrogate preclinical model for high-risk human papillomavirus (HPV) infections, the SfPV1/rabbit model has been widely used to study viral–host interactions and has played a pivotal role in the successful development of three prophylactic virus-like particle vaccines. In this review, we will focus on the use of the model to gain a better understanding of viral pathogenesis, gene function and host immune responses to viral infections. We will discuss the application of the model in HPV-associated vaccine testing, in therapeutic vaccine development (using our novel HLA-A2.1 transgenic rabbits) and in the development and validation of novel anti-viral and anti-tumour compounds. Our goal is to demonstrate the role the SfPV1/rabbit model has played, and continues to play, in helping to unravel the intricacies of papillomavirus infections and to develop tools to thwart the disease. This article is part of the theme issue ‘Silent cancer agents: multi-disciplinary modelling of human DNA oncoviruses’.

scholarly journals Detection of L1, infectious virions and anti-L1 antibody in domestic rabbits infected with cottontail rabbit papillomavirus

2007 ◽  
Vol 88 (12) ◽  
pp. 3286-3293 ◽  
Author(s):  
Jiafen Hu ◽  
Lynn R. Budgeon ◽  
Nancy M. Cladel ◽  
Timothy D. Culp ◽  
Karla K. Balogh ◽  
...  
Keyword(s):  
Rabbit Model ◽  
Zealand White Rabbit ◽  
Sylvilagus Floridanus ◽  
Cottontail Rabbit ◽  
Domestic Rabbit ◽  
Domestic Rabbits ◽  
L1 Protein ◽  
Natural Virus

Shope papillomavirus or cottontail rabbit papillomavirus (CRPV) is one of the first small DNA tumour viruses to be characterized. Although the natural host for CRPV is the cottontail rabbit (Sylvilagus floridanus), CRPV can infect domestic laboratory rabbits (Oryctolagus cuniculus) and induce tumour outgrowth and cancer development. In previous studies, investigators attempted to passage CRPV in domestic rabbits, but achieved very limited success, leading to the suggestion that CRPV infection in domestic rabbits was abortive. The persistence of specific anti-L1 antibody in sera from rabbits infected with either virus or viral DNA led us to revisit the questions as to whether L1 and infectious CRPV can be produced in domestic rabbit tissues. We detected various levels of L1 protein in most papillomas from CRPV-infected rabbits using recently developed monoclonal antibodies. Sensitive in vitro infectivity assays additionally confirmed that extracts from these papillomas were infectious. These studies demonstrated that the CRPV/New Zealand White rabbit model could be used as an in vivo model to study natural virus infection and viral life cycle of CRPV and not be limited to studies on abortive infections.

scholarly journals Vaccination of Rabbits with an Adenovirus Vector Expressing the Papillomavirus E2 Protein Leads to Clearance of Papillomas and Infection

2004 ◽  
Vol 78 (1) ◽  
pp. 116-123 ◽  
Author(s):  
Janet L. Brandsma ◽  
Mark Shlyankevich ◽  
Lixin Zhang ◽  
Martin D. Slade ◽  
Edward C. Goodwin ◽  
...  
Keyword(s):  
Vaccine Development ◽  
Recombinant Adenovirus ◽  
Rabbit Model ◽  
Adenovirus Vector ◽  
Hpv Infection ◽  
Premalignant Lesions ◽  
E2 Protein ◽  
Booster Immunization ◽  
Cottontail Rabbit ◽  
Lesion Regression

ABSTRACT Cervical cancer arises from lesions caused by infection with high-risk types of human papillomavirus (HPV). Therefore, vaccination against HPV could prevent carcinogenesis by preventing HPV infection or inducing lesion regression. HPV E2 protein is an attractive candidate for vaccine development because it is required for papilloma formation, is involved in all stages of the virus life cycle, and is expressed in all premalignant lesions as well as some cancers. This study reports vaccination against E2 protein using a rabbit model of papillomavirus infection. A recombinant adenovirus (Ad) vector expressing the E2 protein of cottontail rabbit papillomavirus (CRPV) was tested for therapeutic efficacy in CRPV-infected rabbits. Primary immunization with the Ad-E2 vaccine, compared to immunization with a control Ad vector, reduced the number of papilloma-forming sites from 17 of 45 to 4 of 45. After booster immunization, vaccinated rabbits formed no new papillomas versus an additional 23 papillomas in rabbits that received the control vector. Papillomas in the Ad-E2 vaccinees were significantly smaller than those in the control rabbits, and all four papillomas in the Ad-E2 vaccinated rabbits regressed. No CRPV DNA was detected either in the regression sites or in sites that did not form papillomas, indicating that the vaccination led to clearance of CRPV from all infected sites.

scholarly journals Establishment of a Cottontail Rabbit Papillomavirus/HLA-A2.1 Transgenic Rabbit Model

2007 ◽  
Vol 81 (13) ◽  
pp. 7171-7177 ◽  
Author(s):  
Jiafen Hu ◽  
Xuwen Peng ◽  
Lynn R. Budgeon ◽  
Nancy M. Cladel ◽  
Karla K. Balogh ◽  
...  
Keyword(s):  
Rabbit Model ◽  
Human Papillomaviruses ◽  
Human Major Histocompatibility Complex ◽  
Class I Mhc ◽  
Mhc I ◽  
Transgenic Rabbit ◽  
Cottontail Rabbit ◽  
Transgenic Rabbits ◽  
Hla A2.1

ABSTRACT Three transgenic rabbit lines that express a well-characterized human major histocompatibility complex class I (MHC-I) gene (HLA-A2.1) have been established. All three lines carry the HLA-A2.1 heavy chain and are able to pass the transgene to their offspring with both the outbred and the inbred EIII/JC genetic background. HLA-A2.1 colocalizes exclusively with rabbit MHC-I on the cell surfaces. These HLA-A2.1 transgenic rabbits demonstrated infection patterns similar to those found after cottontail rabbit papillomavirus (CRPV) challenge when compared with results in normal rabbits, although higher regression rates were found in HLA-A2.1 transgenic rabbits. Because the CRPV genome can accommodate significant modifications, the CRPV/HLA-A2.1 rabbit model has the potential to be used to screen HLA-A2.1-restricted immunogenic epitopes from human papillomaviruses in the context of in vivo papillomavirus infection.

scholarly journals Antisense Oligonucleotide-Based Therapy of Viral Infections

Pharmaceutics ◽  
2021 ◽  
Vol 13 (12) ◽  
pp. 2015
Author(s):  
Woan-Yuh Tarn ◽  
Yun Cheng ◽  
Shih-Han Ko ◽  
Li-Min Huang
Keyword(s):  
Antisense Oligonucleotide ◽  
Viral Infections ◽  
Vaccine Development ◽  
Genetic Disorders ◽  
Rna Degradation ◽  
Short Oligonucleotide ◽  
Host Interactions ◽  
Antiviral Therapies ◽  
Delivery Options ◽  
Target Rna

Nucleic acid-based therapeutics have demonstrated their efficacy in the treatment of various diseases and vaccine development. Antisense oligonucleotide (ASO) technology exploits a single-strand short oligonucleotide to either cause target RNA degradation or sterically block the binding of cellular factors or machineries to the target RNA. Chemical modification or bioconjugation of ASOs can enhance both its pharmacokinetic and pharmacodynamic performance, and it enables customization for a specific clinical purpose. ASO-based therapies have been used for treatment of genetic disorders, cancer and viral infections. In particular, ASOs can be rapidly developed for newly emerging virus and their reemerging variants. This review discusses ASO modifications and delivery options as well as the design of antiviral ASOs. A better understanding of the viral life cycle and virus-host interactions as well as advances in oligonucleotide technology will benefit the development of ASO-based antiviral therapies.

scholarly journals Treatment potential of LPCN 1144 on liver health and metabolic regulation in a non-genomic, high fat diet induced NASH rabbit model

2021 ◽  
Author(s):  
P. Comeglio ◽  
E. Sarchielli ◽  
S. Filippi ◽  
I. Cellai ◽  
G. Guarnieri ◽  
...  
Keyword(s):  
Hepatic Fibrosis ◽  
High Fat Diet ◽  
Metabolic Regulation ◽  
Therapeutic Potential ◽  
Rabbit Model ◽  
Free Testosterone ◽  
Preclinical Model ◽  
High Fat ◽  
Liver Health ◽  
Metabolic Dysfunctions

Abstract Purpose Low free testosterone (T) level in men is independently associated with presence and severity of Non-Alcoholic Steatohepatitis (NASH). The histological and molecular effects of oral testosterone prodrug LPCN 1144 treatment on hepatic fibrosis and NASH features are unknown. A metabolic syndrome-induced NASH model in rabbits consuming high fat diet (HFD) has been previously used to assess treatment effects of injectable T on hepatic fibrosis and NASH features. Here we present results on LPCN 1144 in this HFD-induced, NASH preclinical model. Methods Male rabbits were randomly assigned to five groups: regular diet (RD), HFD, HFD + 1144 vehicle (HFD + Veh), HFD + 1144 (1144), and HFD + 1144 + α-tocopherol (1144 + ALPHA). Rabbits were sacrificed after 12 weeks for liver histological, biochemical and genetic analyses. Histological scores were obtained through Giemsa (inflammation), Masson’s trichrome (steatosis and ballooning), and Picrosirius Red (fibrosis) staining. Results Compared to RD, HFD and HFD + Veh significantly worsened NASH features and hepatic fibrosis. Considering HFD and HFD + Veh arms, histological and biomarker features were not significantly different. Both 1144 and 1144 + ALPHA arms improved mean histological scores of NASH as compared to HFD arm. Importantly, percentage of fibrosis was improved in both 1144 (p < 0.05) and 1144 + ALPHA (p = 0.05) treatment arms vs. HFD. Both treatment arms also reduced HFD-induced inflammation and fibrosis mRNA markers. Furthermore, 1144 treatments significantly improved HFD-induced metabolic dysfunctions. Conclusions Histological and biomarker analyses demonstrate that LPCN 1144 improved HFD-induced hepatic fibrosis and NASH biochemical, biomolecular and histochemical features. These preclinical findings support a therapeutic potential of LPCN 1144 in the treatment of NASH and of hepatic fibrosis.

scholarly journals Chikungunya and Zika Viruses: Co-Circulation and the Interplay between Viral Proteins and Host Factors

Pathogens ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 448
Author(s):  
Sineewanlaya Wichit ◽  
Nuttamonpat Gumpangseth ◽  
Rodolphe Hamel ◽  
Sakda Yainoy ◽  
Siwaret Arikit ◽  
...  
Keyword(s):  
Antiviral Drug ◽  
Virus Transmission ◽  
Antiviral Agent ◽  
Viral Proteins ◽  
Targeted Therapeutics ◽  
Limited Information ◽  
Mosquito Vectors ◽  
Host Proteins ◽  
Host Interactions ◽  
Viral Host Interactions

Chikungunya and Zika viruses, both transmitted by mosquito vectors, have globally re-emerged over for the last 60 years and resulted in crucial social and economic concerns. Presently, there is no specific antiviral agent or vaccine against these debilitating viruses. Understanding viral–host interactions is needed to develop targeted therapeutics. However, there is presently limited information in this area. In this review, we start with the updated virology and replication cycle of each virus. Transmission by similar mosquito vectors, frequent co-circulation, and occurrence of co-infection are summarized. Finally, the targeted host proteins/factors used by the viruses are discussed. There is an urgent need to better understand the virus–host interactions that will facilitate antiviral drug development and thus reduce the global burden of infections caused by arboviruses.

scholarly journals A Unique Protein Self-Assembling Nanoparticle with Significant Advantages in Vaccine Development and Production

2020 ◽  
Vol 2020 ◽  
pp. 1-10 ◽  
Author(s):  
Daniel C. Carter ◽  
Brenda Wright ◽  
W. Gray Jerome ◽  
John P. Rose ◽  
Ellen Wilson
Keyword(s):  
Preliminary Analysis ◽  
Vaccine Development ◽  
Regulatory Protein ◽  
Particle Surface ◽  
Therapeutic Vaccine ◽  
Nonstructural Proteins ◽  
Cell Infection ◽  
Self Assembling ◽  
Unique Protein ◽  
Immunogenic Properties

Nanoparticles are playing an increasingly powerful role in vaccine development. Here, we report the repurposing of nonstructural proteins 10 and 11 (hereafter NSP10) from the replicase polyprotein 1a (pp1a) of the human SARS coronavirus (severe acute respiratory syndrome) as a novel self-assembling platform for bioengineered nanoparticles for a variety of applications including vaccines. NSP10 represents a 152 amino acid, 17 kD zinc finger transcription/regulatory protein which self-assembles to form a spherical 84 Å diameter nanoparticle with dodecahedral trigonal 32 point symmetry. As a self-assembling nanoparticle, NSP10 possesses numerous advantages in vaccine development and antigen display, including the unusual particle surface disposition of both the N- and C-termini. Each set of N- or C-termini is spatially disposed in a tetrahedral arrangement and positioned at optimal distances from the 3-fold axes (8-10 Å) to nucleate and stabilize the correct folding of complex helical or fibrous trimeric receptors, such as those responsible for viral tropism and cell infection. An application example in the exploratory development of a therapeutic vaccine for idiopathic pulmonary fibrosis (IPF), including preliminary analysis and immunogenic properties, is presented. The use of this system could accelerate the discovery and development of vaccines for a number of human, livestock, and veterinary applications.

scholarly journals Immune Response to Herpes Simplex Virus Infection and Vaccine Development

Vaccines ◽  
2020 ◽  
Vol 8 (2) ◽  
pp. 302 ◽  
Author(s):  
Anthony C. Ike ◽  
Chisom J. Onu ◽  
Chukwuebuka M. Ononugbo ◽  
Eleazar E. Reward ◽  
Sophia O. Muo
Keyword(s):  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Viral Infections ◽  
Recombinant Dna ◽  
Vaccine Development ◽  
The Body ◽  
Effective Vaccine ◽  
Subunit Vaccines ◽  
Simplex Virus ◽  
Hsv Infections

Herpes simplex virus (HSV) infections are among the most common viral infections and usually last for a lifetime. The virus can potentially be controlled with vaccines since humans are the only known host. However, despite the development and trial of many vaccines, this has not yet been possible. This is normally attributed to the high latency potential of the virus. Numerous immune cells, particularly the natural killer cells and interferon gamma and pathways that are used by the body to fight HSV infections have been identified. On the other hand, the virus has developed different mechanisms, including using different microRNAs to inhibit apoptosis and autophagy to avoid clearance and aid latency induction. Both traditional and new methods of vaccine development, including the use of live attenuated vaccines, replication incompetent vaccines, subunit vaccines and recombinant DNA vaccines are now being employed to develop an effective vaccine against the virus. We conclude that this review has contributed to a better understanding of the interplay between the immune system and the virus, which is necessary for the development of an effective vaccine against HSV.

Plasmodium knowlesi: a relevant, versatile experimental malaria model

Parasitology ◽  
2016 ◽  
Vol 145 (1) ◽  
pp. 56-70 ◽  
Author(s):  
ERICA M. PASINI ◽  
ANNE-MARIE ZEEMAN ◽  
ANNEMARIE VOORBERG-VAN DER WEL ◽  
CLEMENS H. M. KOCKEN
Keyword(s):  
Parasite Species ◽  
Vaccine Development ◽  
Plasmodium Knowlesi ◽  
Host Interactions ◽  
Model Studies ◽  
Human Red Blood Cells ◽  
Malaria Model ◽  
Human Primate

SUMMARYThe primate malariaPlasmodium knowlesihas a long-standing history as an experimental malaria model. Studies using this model parasite in combination with its various natural and experimental non-human primate hosts have led to important advances in vaccine development and in our understanding of malaria invasion, immunology and parasite–host interactions. The adaptation to long-termin vitrocontinuous blood stage culture in rhesus monkey,Macaca fascicularisand human red blood cells, as well as the development of various transfection methodologies has resulted in a highly versatile experimental malaria model, further increasing the potential of what was already a very powerful model. The growing evidence thatP. knowlesiis an important human zoonosis in South-East Asia has added relevance to former and future studies of this parasite species.

Sign in / Sign up

Export Citation Format

Share Document