C-terminal truncation of the transmembrane protein of an attenuated lentiviral vaccine alters its in vitro but not in vivo replication and weakens its potential pathogenicity.

Preliminary studies revealed that the gene of the gp45 transmembrane protein (TM) of the attenuated equine infectious anemia virus (EIAV) vaccine strain EIAV(FDDV13) had a high frequency of a premature stop codon at position 261W, which generated a 154-residue truncation at the C-terminus. EIAV(FDDV-TM36), a recombinant virus with the TM truncated at the intracytoplasmic (CT) domain due to the presence of a stop codon, was constructed based on EIAV(FDDV)3-8, which is a proviral derivative of the vaccine. EIAV(FDDV-TM36) had a significantly reduced replication capability compared to EIAV(FDDV)3-8 in equine or donkey monocyte-derived macrophages and a decreased ability to induce apoptosis. However, both viruses raised a similar plasma viral load in inoculated horses and did not induce clinical symptoms of EIA. To further compare the in vivo behavior between EIAV(FDDV-Tm36) and EIAV(FDDV)3-8, inoculated horses were transiently immunosuppressed with dexamethasone. While three of the four horses inoculated with EIAV(FDDV)3-8 demonstrated significant increases in viral loads after the drug treatment, none of the four horses inoculated with EIAV(FDDV-TM36) showed a statistically increased plasma viral load. Significantly increased neutralizing antibody levels were also observed in the group of horses inoculated with EIAV(FDDV)3-8, but not EIAV(FDDV-TM36), after immunosuppression. Our results indicate that although the CT truncation of TM decreased viral replication in cultivated equine and donkey macrophages, the primary target cell of EIAV, and did not influence the plasma viral load of inoculated hosts, it weakened the potential pathogenicity of the vaccine. The host immunity is presumably responsible for the equal in vivo replication levels of viruses with either the CT-truncated or prototype TM. Crown Copyright (C) 2011 Published by Elsevier B.V. All rights reserved.