Peste Des Petits Ruminants in Atypical Hosts and Wildlife: Systematic Review and Meta-Analysis of the Prevalence between 2001 and 2021.

Peste des petits ruminants (PPR) or goat plague is considered a leading, highly contagious, and most lethal infectious viral disease of small ruminants affecting the worldwide livestock economy and international animal trade. Although sheep and goats are the primarily affected, the PPR Virus (PPRV) host range has expanded to other livestock (large ruminants) and wildlife animals over the last few decades, resulting in serious concern to the ongoing PPR global eradication program, which is primarily optimized, designed, and targeted towards accessible sheep and goat population. A systematic review and meta-analysis study was conducted to estimate the prevalence and spill-over infection of PPRV in large ruminants (bovine and camel) and wildlife. Published articles from 2001 to October 2021 on the "PPR" were searched in four electronic databases of PubMed, Scopus, Science direct, and Google Scholars. The articles were then selected using inclusion criteria (detection/prevalence of PPRV in bovine, camel, and wildlife population), exclusion criteria (only sheep or goats, lack of prevalence data, experimental trial, test evaluation, and reviews written in other languages or published before 2001), and the prevalence was estimated by random effect meta-analysis model. In the current study, all published articles belonged to Africa and Asia. The overall pooled prevalence of PPR estimates was 24% (95% CI: 15-33), with 30% in Asia (95% CI: 14-49) and 20% in Africa (95% CI: 11-30). The overall estimated pooled prevalence at an Africa-Asia level in bovine and camel was 13% (95% CI: 8-19), and in wildlife, it was 52% (95% CI: 30-74) with significant heterogeneity (I2 = 97%) in most pooled estimates with a high prevalence in atypical hosts and wildlife across Asia and Africa. Over the last two decades, the host range has increased drastically in the wildlife population, even for prevalent PPR in the unnatural hosts only for a short time, contributing to virus persistence in multi-host systems with an impact on PPR control and eradication program. This observation on the epidemiology of the PPRV in unnatural hosts demands appropriate intervention strategies, particularly at the livestock-wildlife interface.

AAV-mediated RLBP1 gene therapy improves the rate of dark adaptation in Rlbp1 knockout mice.

Recessive mutations in RLBP1 cause a form of retinitis pigmentosa in which the retina, before its degeneration leads to blindness, abnormally slowly recovers sensitivity after exposure to light. To develop a potential gene therapy for this condition, we tested multiple recombinant adeno-associated vectors (rAAVs) composed of different promoters, capsid serotypes, and genome conformations. We generated rAAVs in which sequences from the promoters of the human RLBP1, RPE65, or BEST1 genes drove the expression of a reporter gene (green fluorescent protein). A promoter derived from the RLBP1 gene mediated expression in the retinal pigment epithelium and Müller cells (the intended target cell types) at qualitatively higher levels than in other retinal cell types in wild-type mice and monkeys. With this promoter upstream of the coding sequence of the human RLBP1 gene, we compared the potencies of vectors with an AAV2 versus an AAV8 capsid in transducing mouse retinas, and we compared vectors with a self-complementary versus a single-stranded genome. The optimal vector (scAAV8-pRLBP1-hRLBP1) had serotype 8 capsid and a self-complementary genome. Subretinal injection of scAAV8-pRLBP1-hRLBP1 in Rlbp1 nullizygous mice improved the rate of dark adaptation based on scotopic (rod-plus-cone) and photopic (cone) electroretinograms (ERGs). The effect was still present after 1 year.