Tandem mass spectrometry of receptor peptides yielded partial amino acid sequences that allowed the identification of cDNA clones corresponding to the A39R receptor, called VESPR, The VESPR protein contains 1,568 amino acids and has a molecular mass of approximately 200 kD. Sequence analysis indicated that VESPR is a transmembrane glycoprotein and a member of the plexin family. Additional sequence analysis identified a semaphorin-like domain within this family, suggesting an evolutionary relationship between receptor and ligand. VESPR transcript in brain, lung, spleen, and placenta, and an approximately 7.5-kb VESPR transcript in heart. A39R upregulated ICAM1 on, and induced cytokine production from, human monocytes, suggesting that this viral protein can function as an immune modulator during virus infection.