Evaluation of the Replication, Pathogenicity, and Immunogenicity of Avian Paramyxovirus (APMV) Serotypes 2, 3, 4, 5, 7, and 9 in Rhesus Macaques

Khattar, Sunil K.; Nayak, Baibaswata; Kim, Shin-Hee; Xiao, Sa; Samal, Sweety; Paldurai, Anandan; Buchholz, Ursula J.; Collins, Peter L.; Samal, Siba K.

The APMVs belong to family Paramyxoviridae, a large and diverse family that includes viruses from a wide variety of mammalian, avian, reptilian, and fish species around the world [6] . Some members of the family are responsible for major human and animal diseases, while others cause inapparent infections. Paramyxoviruses are pleomorphic and enveloped and contain a non-segmented, negative-sense, single-stranded RNA genome of 13-19 kb. On the basis of virus structure, genome organization and sequence relatedness, the family Paramyxoviridae is divided in to two subfamilies: Paramyxovirinae and Pneumovirinae [6] . The subfam-ily Paramyxovirinae is divided into five genera: Respirovirus (including Sendai virus and human parainfluenza virus types 1 and 3), Rubulavirus (including parainfluenza virus 5 [previously known as simian virus type 5], mumps virus, and human parainfluenza virus types 2 and 4), Morbillivirus (including measles and canine distemper viruses), Henipavirus (comprising Hendra and Nipah viruses), and Avulavirus (comprising the APMVs). Subfamily Pneumovirinae contains two genera, Pneumovirus (including human and bovine respiratory syncytial viruses) and Metapneumovirus (comprising human metapneumovirus and the avian metapneumoviruses) [6, 7] Although a lot of information is available for APMV-1, much less is known about the molecular biology, pathogenicity and host range of the other APMV serotypes. As an initial step towards their characterization, we have recently determined the complete genome sequences of APMV-2 to -9 [8] [9] [10] [11] [12] [13] [14] [15] and we have developed reverse genetics systems for APMV-2, -3, -4 and -7 [16] [17] [18] [19] . However, the biological characteristics and pathogenicity of APMV-2 to -9 remain poorly understood. APMV-2 has been associated with severe respiratory disease, reduced egg production and infertility in turkeys [20, 21] . APMV-3 has been associated with encephalitis and high mortality in caged birds, respiratory disease in turkeys and stunted growth in young chickens [22, 23] . APMV-4 strains have been isolated from chickens, ducks and geese [19] . APMV-5 causes disease in budgerigars that is characterized by depression, dyspnoea, diarrhea and high mortality [24] . APMV-6 and -7 cause mild respiratory disease in turkeys and are associated with a drop in egg production [25, 26] . APMV-8 and -9, isolated from ducks, waterfowl, and other wild birds, did not produce any clinical signs of viral infection in chickens [27, 28] In the last 10 years, reverse genetic techniques have made it possible to engineer NDV as a potential vaccine vector for both human and animal uses [29] [30] [31] [32] [33] [34] [35] [36] [37] [38] [39] . NDV vectors expressing a number of foreign antigens have been evaluated not only in avian hosts, but also in murine and nonhuman primate models [29] [30] [31] [32] [33] [40] [41] [42] . Several strains of NDV have been shown to be highly restricted for replication in these mammalian models, indicating that they are highly attenuated due to a strong host range restriction and represent promising vaccine vectors. However, NDV strains are highly related antigenically, and therefore the use of NDV vectors for multiple purposes would be compromised by the induction of vector-specific immunity. This limitation might be overcome by using other APMV serotypes that are antigenically distinct from NDV as alternative vaccine vectors. In addition, it is possible that one or