TM DOMAIN SWAPPING OF MURINE LEUKEMIA-VIRUS AND HUMAN T-CELL LEUKEMIA-VIRUS ENVELOPES CONFERS DIFFERENT INFECTIOUS ABILITIES DESPITE SIMILAR INCORPORATION INTO VIRIONS

We investigated the influence of transmembrane protein (TM) domains on incorporation of retroviral envelopes into virions and on infectivity . We introduced complete, truncated, or chimeric Friend murine leukemi a virus (F-MuLV) and human T-cell leukemia virus type 1 (HTLV-1) envel opes into an MuLV particle-producing complementation fell line. As sho wn previously for HTLV-1 envelopes containing extracellular domains of F-MuLV TM (C. Denesvre, P. Sonigo, A. Corbin, H. Ellerbrok, and M. Si tbon, J. Virol. 69:4149-4157, 1995), reverse chimeric F-MuLV envelopes containing the extracellular domain of HTLV-1 TM were not processed, In contrast, a chimeric MuLV envelope containing the entire HTLV membr ane-spanning and cytoplasmic domains (FHTMi) was efficiently processed , fusogenic as tested in a cell-to-cell assay, and efficiently. incorp orated into MuLV particles. However, these MuLV particles bearing FHTM i envelope proteins could not infect mouse or rat cells which are susc eptible to wild-type F-MuLV. Therefore, envelopes, which are readily f usogenic in cell-to-cell assays and also efficiently incorporated into virions may not necessarily confer virus-to-cell fusogenicity. HTLV e nvelopes, whether parental, chimeric (containing the MuLV cytoplasmic tail) or with a truncated cytoplasmic domain, were incorporated into M uLV particles with equal efficiencies, indicating that the cytoplasmic tails of these envelopes did not determine their incorporation into v irions. In contrast to FHTMi envelope, HTLV-1 envelopes with F-MuLV me mbrane-spanning and cytoplasmic domains, as well as wild-type HTLV-1 e nvelopes, conferred virion infectivity, These results help to define r equirements for envelope incorporation into retroviral particles and t heir cell-free infectivity.