A Reverse Genetics Approach for the Design of Methyltransferase-Defective Live Attenuated Avian Metapneumovirus Vaccines
Avian metapneumovirus (aMPV), also known as avian pneumovirus or turkey rhinotracheitis virus, is the causative agent of turkey rhinotracheitis and is associated with swollen head syndrome in chickens. aMPV belongs to the family Paramyxoviridae which incl
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Introduction Avian metapneumovirus (aMPV), also known as avian pneumovirus (APV) or turkey rhinotracheitis virus, is an economically important pathogen that causes an acute, highly contagious respiratory disease in turkeys and is the etiological agent of “swollen head syndrome” in chickens [1, 2]. Since the isolation of aMPV in South Africa in 1978, the virus has become prevalent worldwide [1–4]. Based on antigenicity and genetic diversity, four subtypes of aMPV, designated A, B, C, and D, have been characterized [2]. Subtypes A, B, and D are found mainly in Europe and Asia [3–6]. In the USA, aMPV was first identified in 1996, in a commercial turkey flock with respiratory disease in Colorado [7]. The virus was classified as subtype C due to low sequence identity to subtype A and B viruses [7–9]. Subsequently, it emerged in turkey flocks in Minnesota and became a major problem in the turkey industry in the USA [8–12]. Epidemiological studies suggest that aMPV subtype C is distributed in a wide range of avian species such as chickens, ducks, geese, American crows, cattle egrets, American coots, and pigeons. A recent phylogenetic analysis showed that two distinct sub-lineages of aMPV subtype C exist in the USA [11]. Clinical signs of aMPV in turkeys are characterized by coughing, sneezing, nasal discharge, and swollen infraorbital sinuses. Infected flocks have high morbidity (50–100 %) at all ages, with mortality ranging from 0.5 % in adult turkeys to 80 % in young poultry [6–11]. Direct economic losses caused by this virus include poor weight gain, sharply reduced egg production, poor egg quality, and high morbidity and mortality.
Sunil Thomas (ed.), Vaccine Design: Methods and Protocols, Volume 2: Vaccines for Veterinary Diseases, Methods in Molecular Biology, vol. 1404, DOI 10.1007/978-1-4939-3389-1_7, © Springer Science+Business Media New York 2016
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aMPV is a non-segmented negative-sense (NNS) RNA virus, belonging to the genus Metapneumovirus in the subfamily Pneumovirinae of the family Paramyxoviridae. The only other member in the genus Metapneumovirus is human metapneumovirus (hMPV), which was first identified in infants and children with acute respiratory tract infections in 2001 in the Netherlands [13]. Soon after its discovery, hMPV was recognized as a globally prevalent pathogen and is a major causative agent of acute respiratory tract disease in individuals of all ages, especially infants, children, the elderly, and immunocompromised individuals [14, 15]. Interestingly, aMPV subtype C shares more homology with hMPV than the other three aMPV subtypes. In addition, turkeys were shown to be susceptible to hMPV infection [16]. Paramyxoviruses include many other important human pathogens such as human respiratory syncytial virus (RSV), human parainfluenza virus type 3 (PIV3), measles virus, and mumps virus. The family also contains highly lethal emerging pathogens such as Nipah virus and Hendra virus, as well as agriculturally important viruses such as Newcastle disease virus (NDV
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