Specific Roles for Lipids in Virus Fusion and Exit Examples from the Alphaviruses - Fusion of Biological Membranes and Related Problems - page 413

The capsid and spike polypeptides are synthesized as a polyprotein
from a subgenomic RNA, in the order capsid-p62-6K-E1, and are post-
translationally processed to produce the individual polypeptides (Strauss
and Strauss, 1994; Kielian, 1995; Garoff et al., 1994; Schlesinger and
Schlesinger, 1986). p62 (termed PE2 in SIN) is a precursor to the mature
E3 and E2 subunits. 6K is a small hydrophobic peptide that provides the
signal sequence for El and is found at low levels in the mature virus parti-
cle. During virus infection, capsid protein is synthesized on free ribosomes,
cleaves itself autoproteolytically from the nascent polypeptide chain, and
assembles with viral RNA to form new nucleocapsids (Figure 2). A signal
sequence on p62 then initiates translocation of the remainder of the
polyprotein into the lumen of the rough endoplasmic reticulum (RER).
The El and p62 subunits associate within the RER to form non-covalent
heterodimers, and are transported as a complex through the RER and
Golgi to the plasma membrane. Evidence suggests that this dimerization is
required for proper spike protein folding and transport. Similar to cellular
membrane proteins, El and p62 are glycosylated and fatty acylated during
their transport through the RER and Golgi complex. The p62 precursor is
cleaved after an ArgHisArgArg sequence to give E3 and E2. Cleavage
probably occurs in or after the trans-Golgi network by the cellular protease
furin (deCurtis and Simons, 1988; Strauss and Strauss, 1994). Following
arrival at the plasma membrane, the spike proteins interact with the viral
nucleocapsid via the E2 cytoplasmic domain to mediate the budding and
release of progeny virus particles.
2.2. Virus Entry and Fusion
2.2.1. Endocytic Entry and Low pH-Triggered Fusion
SFV was the first virus demonstrated to infect cells via endocytic
uptake and low pH-triggered fusion (Helenius et al., 1980) (Figure 2), an
overall pathway now known to be used by members of a number of virus
families including orthomyxoviruses (Bentz, 1993; White, 1992; Wiley and
Skehel, 1987), rhabdoviruses (Lenard, 1993), flaviviruses (Allison et al.,
1995), bunyaviruses (Gonzalez-Scarano, 1984), and adenoviruses (Greber
et al., 1993). The first step in alphavirus entry is the binding of virus to recep-
tors on the plasma membrane. Receptor binding appears to occur primarily
through the E2 subunit (Kielian, 1995; Strauss and Strauss, 1994), although
there may be some involvement of the El subunit as well. Several mole-
cules have been proposed as candidates for alphavirus receptors, including
proteins such as the high affinity laminin receptor and class I major histo-
compatibility antigens (Wang et al., 1992; Ubol and Griffin, 1991; Helenius