Small ruminant lentivirus genetic subgroups associate with sheep TMEM154 genotypes

Area of Science:

• Veterinary Virology
• Animal Genetics
• Sheep Production

Background:

• Small ruminant lentiviruses (SRLVs) cause significant economic losses in the U.S. sheep industry.
• Sheep's genetic makeup, specifically variations in the ovine transmembrane 154 gene (TMEM154), affects their susceptibility to SRLV infection.
• Two TMEM154 haplotypes encoding glutamate at position 35 (E35) increase infection risk compared to the lysine (K35) haplotype.

Purpose of the Study:

• To characterize SRLVs circulating in U.S. sheep from a diverse Midwestern flock.
• To investigate the association between SRLV genetic subgroups and TMEM154 E35K genotypes in sheep.
• To understand how host and viral genetics interact to influence SRLV infection risk.

Main Methods:

• Proviral DNA amplification and sequencing of the gag and env genes from SRLV isolates.
• Phylogenetic analysis to determine SRLV genetic subgroups.
• Statistical association testing between SRLV subgroups and TMEM154 E35K genotypes.

Main Results:

• SRLVs from the studied flock clustered into two distinct subgroups (1 and 2), separate from European strains.
• SRLV subgroup 1 was significantly associated with TMEM154 K35 genotypes (gag p<0.001, env p=0.01).
• SRLV subgroup 2 was significantly associated with TMEM154 E35 genotypes (gag p<0.001, env p=0.01).

Conclusions:

• U.S. SRLVs have evolved to preferentially infect sheep with specific TMEM154 E35K genotypes.
• Both ovine host genetics (TMEM154 genotype) and SRLV genetic subgroup play a crucial role in determining infection risk.
• These findings have implications for managing SRLV in sheep populations by considering both host and viral factors.