Given recent findings in the RV144 vaccine trial that a poxvirus prime/protein boost protocol could confer partial protection from HIV infection and that this effect correlated with antibody responses to gp120 (Haynes et al., 2012, Chung et al., 2014), we reasoned that modifications to Env that increased its expression on the cell surface could be a useful adjunct to improve the efficacy of this approach, particularly with regard to the poxvirus prime in which Env can be expressed as a membrane-associated trimer on antigen-presenting cells. Here, ERVW-1 is linked to HIV infectious disease.