Veterinary diseases
Avian
Avian influenza virus (AIV): Avian influenaze viruses (AIV) are negative-sense isngle-stranded segmented genomes. They are encapsulated by envelopes containg the surface proteins hemagglutinin (HA) and neuraminidase (N) and are classified by 16 identified HA and ( NA subtypes, all of which occur in their reservoir hosts, free-flying waterfowl and shorebirds. The roles of birds as reservoire hosts in which viruses with pandemic potential can be amplified and trasnmited to humans have beocme a focus of itnerest with the emergence of HSN1 highly pathogenic AIV.
Poultry all over the world ahve been threatened since the appearance of highly pathogenic avian influenze viurs HSN1. The WHO has enoucraged the use of poultry vaccination policy together with biosecurity measures to counteract H5N1 outbreaks. High levels of hemagglutination inhibition antibodies and protection have been acheived using a DNA vaccine based on C3d molecule fused to HA in mice and enhanced chicken immunity by adminstiering a recombinant adenovial vector containing the HA H5 fused to chicken 154 has been acheived. (Pose, Veterminary Microbiology, (2001), 328-337).
Adams (Molecular Immunoloy 46 (2009) 1744-1749) discloses that duck and chicken are important hosts of AIV, with distinctive response to infection. They examined the expression of cytokine genes in response to low pathogenic AIV H11N9 infection in PBMCs isolated from the blood of ckien and ducks.
Infectious bronchitis virus (IBV): has been a continuing problem in poultry for more than 70 years. IBV cuases a highly contagious respiratory disease in chickens, resembles the recently described severe acute respirtory virus in pathogeneis and gehome oranization. It has been shown that the SARS in humans is caused by a coronavirus that resembles infectious bronchitis in transmission, pathogenesis and genome structure. Vaccines are available, but they are not effective long-eterm in controlling IBV infection, especially for variant strains. Genetic variations are ocmmon in new strains because of both point mutations and recombinants. CD8+ T cells are critical in controlling acute IBV infection. Adoptive transfer of T cells collected at 10 days post-infection protected syngenic chicks from clinical illness. Innate immunity may also be intstrumental in that chicken IFN-1 inhibits IBV replication in vivo. Local adminsitration of IFN-I also inhibited IBV associated respiratory illness. (Pei, Developmental and Comparative Immunology 29 (2005) 153-160).
Horses
Recurrent airway obstruction (RAO): is a respiratory condition of horses that is characterized by bronchospasm, peribronchial cell infiltration, and accumulation of a predominantly neutrophilic exudate in the lumen of the small airways. Inflammation of the small airways in horses with RAO results from inhalation of airborne particles (mainly molds and fungi). Thus, control of environmental dust is very important to the treatment of horses with RAO. Treatment also commonly includes corticosteroids. Pentoxifylline (PTX) which is a methlxanthine derviative that is a nonselelctive inhibitor of phosphodiesterases (PDE) has also been reproted to improve respriatory function of RAO affected horses (Leguillette, AJVR, 63(3), 2002).
Viral respiratory infections: are common in horses and include herpesvirus type 4(EHV-4, rhinopneumonitis), equine influenza and equine viral arteritis. Symptoms include nasal discharge, submandibular lymphadenopathy, anorexia and cough (see Merck Manual, 2011).
Bacterial respiratory infections: such as pneumonia often accompany viral respiratory infections because the viral respirtatory infections destroy respiratory defense mechanisms. Secondary bacterail disease may result in mucosal bacterail infections (rhinitis and tracheitis).
Bovine (Cattle):
Bacterial Infections:
–Mannheimia haemolytica: is the principla bacterium isolated from respiratory disease in feedlot cattle and is a significant component of enzootic pneumonia in all neonatal caovles. A commensal of the nasopharynx. M. haemolytica is an opportunist, gaining access to the lungs when host defesnes are compromised by stress or infection with respirtatory viruses of mycoplasma. Although several serotypes act as commensals, A1 and A6 are the most fequent isolates from pneumonic lungs. Potential virulence factors include iron-regulated outer membrane proteins and leukotoxin (Lkt).
M. haemolytica is a gram-engative, non-motile, nons-spore-forming, fermentative, oxidase-postive, facultative anaerobic coccobacillus. It includes 12 capsular seriotypes. Both serotypes A1 and A2 colonize the upper respiratory tract of cattle and sheep.
Viral Infections:
–Bovine Herpes virus Type-1 (BHV-1)/Bovine Respiratory Disease (BRD): BHV-1, an alpah herpes virus, is an important etiological agent of respirtory and genitcal diseass in cattle. The resptiratory form of the disease spreads via aerosols and is characterized by rhinotracheitis, conjunctivities and development of bovine respitaory disease (BRD) complicated by secondary bacterial infections. The predisposition to bacterial complications by the virus is related directly to its cytolytic effect on the cells of nasla and tracheal mucosa apart from its immunosuppressive effects. The genital infection spreads via genital secretions, semen and foetal fluids. (Kaushik, US 2010/0196375).
(Kaushik (US 2010/0196375) discloses a single chain variable fragmetn (scFv) that includes a light chain, a linker and a heavy chain variable region, that binds BHV-1 virus and methods for treating or netralizing BHV-1 infection.
Rabbits:
Lethal rabbit virus, Rabbit Hemorrhagic Disease Virus type 2 (RHDV2) ontagious among rabbits, RHDV2 has been identified as the cause of death in several cases after tests conducted by the Washington Animal Disease Diagnostic Laboratory at Washington State University came back positive. In 2019, the disease claimed the lives of numerous domestic and feral rabbits in Island and Clallam counties. Originally considered a foreign animal disease, eliciting immediate restrictions and emergency actions, RHDV2 is now regarded as a stable-endemic issue within Washington.
Citrus:
Bacteria Candidatus Liberibacter asiaticus (CLas): is the etiological agent responsible for huanglongbing (HLB) disease in cittrus. The Asian citrus psyllid (ACP), Diaphorina citri (Hemiptera: Liviidae) is the vector of the bacterial CLas. HLB is the most destructive citrus disease worldwide, cuaisng fruit from infected tress to become small, misshapen and discolored with unpleasnt bitter and acidic flavor The damage caused by HLB is extensive, decreasing furit produciton by 57% in Florida alone form 2004-2019 and causing an estimated 1.7 billion in production losses between the harvest seasons of 2006-2007 and 2010-2011. The initial symptoms of the disease do not appear for months and at first resemble nutrient deficiencies, resulting in HLB infections remaining undiagnosed for long periods and providing stable reservoirs for teh pathogen. HLB is mianly transmitted by the ACP vector, but it can also be spread form tree to tree through grafting diseased branches. (Asban, “CRISPR-Cas9-mediated mutagenesis of the Asian Citrus Psyllid, Diaphorina citri” Gen Biotechnology, 2(4), 2023).
The main method for reducing the spread of HLB among commercial groves includes remvoing infected trees serving as HLB reservoirs, planting certified healthy plants and applying insecticides to control D. citri vector populations. (Asban, “CRISPR-Cas9-mediated mutagenesis of the Asian Citrus Psyllid, Diaphorina citri” Gen Biotechnology, 2(4), 2023).
Asban, (“CRISPR-Cas9-mediated mutagenesis of the Asian Citrus Psyllid, Diaphorina citri” Gen Biotechnology, 2(4), 2023) disloses genetic based control methods similar to those used in other insect vectors of disease and agicultural pests such as Aedes aegypti and Drosophila suzukii. Asban showed CRISPR-Cas9 gene editing in D. citri using embryonic microinjection and ReMOT control. To ensure gene mofidicaiton, they targeted genes with visible mutatant phenotypes, whie (w) and kynurenine hydroxylate (kh). They dientified the locaiton of these genes in the G. citri geneome to design targeting gRNAs, developed and tested Cas9-RNP delivery methods into embryos and females and validated the phenotypic and genotypic changes upon gene disruption. first they idnetified the genomic sequences for w and kh by comparing it with the known protein sequences of the Drosophila melanogaster w and kh using tBastn on the latest version of teh D. citri genome available in the citrusgreening.org platform.