Evolutionary dynamics and oncolytic ability of avian paramyxovirus type-I (APMV-1)

Abstract

Avian paramyxovirus virus type I (APMV1) can infect multiple avian species and cause Newcastle disease (ND) outbreaks in many poultry farms. ND is highly contagious and can cause devastating effects on the economy of the poultry farms. Even with such significant economic importance, not enough data is collected regarding its geographical distribution, host preference, and genetic diversity. Conducting proper evolutionary analysis at the sub-genotype level and getting the epidemiological data can give us insights into the dynamics of this virus.

Systematic surveillance was conducted at live poultry markets (LPMs) and wet-lands to understand the epidemiological and genetic characteristics of the APMV1 in Southern China during 2007-2017. Here, nearly 19,000 APMV1 viruses were identified, among which 50% were from chickens and the remaining from ducks, geese, and wild birds. Regions located at the East-Asia flyway, i.e., coastline and regions near to the Poyang Lake, showing a relatively higher APMV1 isolation rate. Phylogenetically, all the isolates clustered with the previously reported Class I (70%) and Class II (30%) AMPV1. ClassI-Id was never reported apart from North America; rather, it was identified in ducks near the Poyang Lake. A novel genotype isolated in wild and domestic ducks was designated as ClassI-Ic.i. Considering proper biosafety controls during vaccinations, limiting interactions of backyard poultry with wild birds, and isolating different bird species in LPMs may alleviate the risk for virus transmission and disease outbreak.

Irrespective of having its adverse role in the poultry industry, APMV-1 has gained popularity among researchers for its oncolytic ability. To date, not many APMV-1 strains have been documented for the oncolytic work. In this study, APMV-1 strains from our archived isolates were screened and evaluated them for obtaining a better candidate. A screening of 34 archived APMV-1 strains for their oncolytic ability at the in-vitro level was conducted. The underlying mechanism that caused the lysis of lung cancer cells remains unexplored. APMV-1 has a versatile therapeutic ability, it can not only lyse the cells but also it can initiate the anti-tumor immunity within the host.

An animal model was developed having a double tumor model. Oncolytic viral therapy to one tumor (primary) was provided and looked into the effect on the secondary or untreated tumor. The promising outcomes showed the regression in the tumor size was comparatively better in HK-84 treated mice than the positive control mice. The survivability of mice was 100% in virus treatment compared to control mice (60% and 80% for cisplatin and PBS treated mice, respectively). Very little information is available regarding the immuno-modulations happening within the tumor microenvironment post oncolytic virotherapy. So in this study, a complete transcriptomic profile of the tumors and blood samples obtained from mice post oncolytic treatment was established. Significant anti-tumor immune upregulations in oncolytic virus-treated mice compared to the positive control (cisplatin drug-treated) mice was achieved.

APMV-1 is an important field to explore as it has a significant role in the field of agricultural and also its therapeutic contribution to cancer therapy.