Interaction of MA with Env proteins

   MA may also interact with the Env proteins during budding. Portions of MA can be deleted from ASLV and HIV-1 Gag proteins without impairing its ability to assemble and bud from the membrane (Chapter 7). Some of these deletions prevent incorporation of HIV envelope glycoproteins into virions (Yu et al. 1992; Fäcke et al. 1993), suggesting that at least a part of the MA domain forms a contact with the cytoplasmic portion of Env. Such contacts are also indicated by the reported ability of ASLV MA to be cross-linked to Env with bifunctional reagents (Gebhardt et al. 1984) and by mutations in M-PMV MA that suppress a mutation in the carboxy-terminal domain of Env (Brody et al. 1992). Finally, chimeric Gag proteins containing MA from HIV-1 and the remainder from visna virus specifically incorporate the HIV Env protein into budding virions (Dorfman et al. 1994a). In seeming contradiction to the need for specific MA-Env interaction, most or all of the cytoplasmic tail of Env of HIV-1 and ASLV can be deleted without loss of incorporation of the protein into virions and without loss of infectivity (Perez et al. 1987; Wilk et al. 1992). Similarly, retroviruses are well known for their ability to incorporate into infectious virions (called pseudotypes) envelope proteins from retroviruses in other genera and even from other viral families. The best studied pseudotypes are those with the vesicular stomatitis virus (VSV) G protein (Zavada 1972; Huang et al. 1973; Love and Weiss 1974; Emi et al. 1991). An ASLV genome has been engineered to carry the gene for influenza virus hemagglutinin in place of env, and the resulting virus is infectious at a low level (Dong et al. 1992). Since the carboxy-terminal domains of these diverse transmembrane proteins show no obvious sequence similarities, it is unclear what mechanisms select them for inclusion into a virion. The same question underlies the preferential incorporation of certain host-cell membrane proteins into virions. One speculation is that incorporation of plasma membrane proteins into a budding virion occurs when they are highly mobile and not tethered to the cytoskeleton as are many cellular membrane proteins (Chapter 7).