Biology Reference
In-Depth Information
Hantaan hantavirus, for example (DeTulleo and Kirchhausen, 1998; Helenius
et al
., 2004). Macropinocytosis is another
endocytosis pathway utilized by viruses belonging to vaccinia, adeno, picorna,
and other virus families. Macropinocytosis is an endocytic mechanism normally
involved in fluid uptake induced by growth factors, phorbol ester. However, the
binding of virus particles can also activate signaling pathways that trigger actin-
mediated membrane ruffling and blebbing. This is followed by the formation of
large vacuoles (macropinosomes) at the plasma membrane, internalization of
virus particles, and penetration by the viruses or their capsids into the cytosol
through the limiting membrane of the macropinosomes (Mayor and Pagano,
2007; Mercer and Helenius, 2009). A variety of evidences suggest that macro-
pinocytosis can be a mechanism for HIV-1 and Epstein-Barr herpes virus entry in
some primary cells or cell lines (Marechal
., 1980; Jin
et al
., 2002; Kee
et al
., 2001; Miller and Hutt-Fletcher,
1992). Based on the more defined criteria of macropinocytosis (Mercer and
Helenius, 2009), these conclusions are probably premature and may depend on
the experimental conditions that use very concentrated viruses which may influ-
ence the utilization of less specific pathways. It should be noted that different
strains of the same virus can elicit dramatically different responses in host cells
during entry, and different macropinocytic mechanisms are possible in the same
cell line through subtle differences in the activating ligand (Mercer
et al
, 2010a).
An additional endocytosis pathway, whilst badly defined, is known
as a clathrin- and caveola-independent pathway. The dependence on different
GTPase and cargo proteins (dynamin, Rho, CDC42, ARF6, etc.) defines
this endocytosis pathway. Several viruses are using this clathrin- and caveola-
independent pathway, including the influenza orthomyxovirus (as a second
possible pathway), the SARS-CoV coronavirus, the lymphocytic choriomenin-
gitis arenavirus (LCMV), and picornaviruses (Madshus
et al.
et al.
, 1987; Matlin
et al.
,
1981; Wang
, 2008). Finally, other vesicles (characterized by caveolin or
caveosome, with a high concentration in cholesterol and sphingolipids) are
clathrin-independent but dynamin-dependent and do not have acid compart-
ments before their merging with early endosomes (Mayor and Pagano, 2007).
The nonenveloped SV40 virus and some human enteroviruses are the prototypes
of the pH-independent viruses that use this endocytosis pathway. So far, only two
enveloped viruses have been described to use this pathway, the Newcastle disease
paramyxovirus (NDV) (Cantin
et al.
, 2007) and Ebola virus (Empig and
Goldsmith, 2002; Sanchez, 2007). Most viruses have been shown to use only
one entry pathway; however, there are more and more recent examples that
indicate that some viruses use multiple endocytosis pathways to enter their target
cells (influenza, HIV). For example, Ebola viruses are known to enter cells by
clathrin-mediated endocytosis (Sanchez, 2007), but lipid raft-associated, caveo-
lin-mediated endocytosis has also been proposed as a mechanism of Ebola virus
uptake (Empig and Goldsmith, 2002).
et al.
