ARS | Publication request: Phylogenetic clades of ovine progressive pneumonia virus (OPPV) associate with sheep TMEM154 genotypes

Submitted to: Meeting Abstract
Publication Type: Abstract Only
Publication Acceptance Date: June 6, 2012
Publication Date: September 11, 2012
Citation: Sider, L.H., Clawson, M.L., Heaton, M.P., Chitko Mckown, C.G., Harhay, G.P., Smith, T.P.L., Leymaster, K.A. 2012. Phylogenetic clades of ovine progressive pneumonia virus (OPPV) associate with sheep TMEM154 genotypes. The 58th Genomic Congress, September 11-14, 2012. Foz de Iguacu, Brazil. Poster No. GM001.

Technical Abstract: Ovine progressive pneumonia virus (OPPV) is a lentivirus within the Retroviridae family that infects sheep. OPPV-induced clinical disease progresses slowly over time and manifests primarily in the lungs and central nervous system. Symptoms include weight loss, respiratory distress, and inevitably death. There are no cures or vaccines for OPPV, which is widespread throughout much of the world. However, haplotypes within the ovine transmembrane protein (TMEM)154 have recently been associated with reduced OPPV susceptibility. Specifically, a TMEM154 haplotype encoding glutamate at position 35 (E35) associates with OPPV infection, whereas a lysine (K35) haplotype does not. Prior to this study, it was not known if TMEM154 genotypes associate with particular OPPV genetic variants. Accordingly, our goals were to 1) phylogenetically characterize OPPV genetic variants from infected sheep with known TMEM154 genotypes and 2) test the variants for an association with TMEM154 genotypes. Two regions of the OPPV genome were targeted for proviral amplification, cloning and sequence analysis. The first was gag, which codes for several viral nucleocapsid structural proteins, and the second was the transmembrane region of env, which codes for a protein complex that extends through the viral envelope. OPPV gag sequences were determined from a collection of 201 OPPV infected sheep that originated from one U.S. location and varied by breed composition and birth year. Phylogenetic analyses of the gag sequences showed that they clustered in two major clades that share a common ancestor, and that they are evolutionarily distinct from OPPV subtypes originating from Europe. One of the clades associated with TMEM154 genotypes consisting of at least one copy of the susceptible TMEM154 E35 haplotype, whereas the other associated with homozygous TMEM154 K35 genotypes (p<0.001). Additionally, env subtypes generated from 57 sheep also placed within one of two major clades that had the same association with TMEM154 genotypes (p=0.049). These results indicate that 1) OPPV genetic subtypes differ by geographical location, and 2) some genetic variants of OPPV are underrepresented in sheep with homozygous TMEM154 K35 genotypes. However, our results also show that a phylogenetic subset OPPV has evolved that can overcome host genetic resistance to infection that associates with TMEM154 K35. Consequently, both host and OPPV genotypes are affecting the occurrence of OPPV infection in sheep.