Biology Reference
In-Depth Information
1
Phagocytosis
Macropinocytosis
4
2
3
5
6
Clathrin-
mediated
endocytose
Caveolin-
mediated
endocytose
Clathrin- and caveolin-
independent entry pathways
CDC42
regulated
ARF6
regulated
RhoA
regulated
Actine
Vaccinia, rubella
Epstein -Barr
HIV, Nipah
Cholesterol
Equine Herpes
HIV?
CCP
Cholesterol
Sphingolipide
Caveolin
Dynamin
RAB5
PKC-
a
-1
RhoA
Dynamin
LCMV
HCV, HBV
TBE, SFV,
VSV
ARF6
RAB11
RAB22
Flotillin - 1
PI3K
Clathrin
Dynamin
Influenza
Sars -CoV
NDV, Ebola
Non enveloped viruses
(SV40, polyomavirus)
CDC42
RAB5
PI3K
Early tubular
recycling
compartment
?
RAB5
RAB5
pH 7
Caveosome
GPI-enriched
early
compartment
(GEEC)
RAB5
Early endosome
Influenza
pH 6-6.5
Late endosome
RAB7
ESCRT
pH 5-6
Rab9
LAMP-1
Golgi, RE
Lysosome
Dead end
Viral receptor
Dynamin
Clathrin
Figure 4.1. Viruses exploit different endocytosis pathways to enter host cells. Multiple mechanisms
have been defined as pinocytic, that is, they are involved in the uptake of fluids, solutes,
and small particles. These include clathrin-mediated, macropinocytosis, caveolar/raft-
mediated mechanisms, as well as several novel mechanisms. Large particles are taken up
by phagocytosis, a process restricted to a few cell types. Though poorly documented, the
entry of some viruses can be mediated by numerous cargoes which can be endocytosed
by mechanisms that are independent of the clathrin coat protein and the fission
GTPase, dynamin. These pathways include RhoA- (IL-2 pathway), ARF6-, and
CDC42-regulated pathway (GEEC pathway). After binding of the particles to the cell
surface entry receptor, genetic material is delivered into the cytoplasm of the cell via a
specific endocytosis pathway. Recently, macropinocytosis has emerged as an important
entry pathway for viruses (1). The entry of most pH-dependent viruses is mediated by
the use of clathrine-coated endocytic vesicles (2). Other viruses penetrate host cells via
the formation of vesicles covered by caveola molecule (3). Using this pathway, the viral
particles are targeted to neutral pH caveosomes or to early endosomes with moderately
acid pH. Alternately, the virus can use non-clathrin, non-caveolin-dependent pathways,
both dynamin-dependent or independent (4, 5, 6). These pathways are differentiated by
the implication of different GTPases (RhoA, CDC42, or ARF6) and their different
compositions (cholesterol, flotillin, TEM, etc).
