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.

We recently showed that APMV-2 to -9 are competent to infect and replicate to low-to-moderate titers in mice and hamsters [37, 38] . However, rodents are uncertain predictors of performance in other species such as humans because it is possible, and indeed likely, that there will be differences in the level of host range restriction between rodents and other species including primates. In the present study, we sought to evaluate the replication and pathogenicity of APMV-2, -3, -4, -5, -7 and -9 in rhesus macaques as a surrogate for humans. The viruses included biologically-and recombinantly-derived wt viruses as well as several recombinant viruses in which the F protein cleavage site had been modified to be multi-basic and to contain the optimal furin protease cleavage site motif RX(R/K)RQ (signature R and K residues underlined). This was done because the presence of a furin motif in the F protein cleavage site typically facilitates cleavage and is a major determinant of virulence for NDV strains [45, 46] , although this paradigm is uncertain for the other APMV serotypes [16, 18, 19] . The present study showed that, except for APMV-5, all of the APMVs under evaluation replicated at varying levels in rhesus macaques without inducing any apparent clinical disease signs. Thus, APMV serotypes 2, 3, 4, 7, and 9 are infectious, replication-competent and attenuated in non-human primates. In future work, the reverse genetics system for APMV-2, -4, and -7 will be used for the development of APMV vectored vaccines.