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infect via the airway epithelia, such as Ebola virus or Influenza virus, may prove
useful for gene therapy of the human airway (Kobinger
., 2001). Exclusive
transduction of retinal pigmented epithelium could be achieved following sub-
retinal inoculations of some vector pseudotypes in rat eyes (Duisit
et al
., 2002).
High transgene expression was detected in dermal fibroblasts transduced with
VSV-G-, EboZ-, or MuLV-pseudotyped HIV vector and effectively targeted
quiescent epidermal stem cells which underwent terminal differentiation result-
ing in transgene expression in their progenies (Hachiya
et al
., 2007). Important-
ly, several viral EnvGP target lentiviral vector to the CNS such as rabies (Wong
et al
et al
., 2004), mokola (Watson
et al
., 2002; Wong
et al
., 2004), lymphocytic
choriomeningitis virus envelope (LCMV) (Miletic
et al
., 2004; Stein
et al
.,
2005), or Ross River (Kang
., 2002) viral EnvGP that even permit transduc-
tion of specific cell types within the CNS. Likewise, screening of a large panel of
pseudotyped vectors established the superiority of the gibbon ape leukemia virus
(GALV) (Sandrin
et al
., 2000) and the cat endogenous
retroviral-modified glycoproteins (RD114) (Sandrin
et al
., 2002; Stitz
et al
., 2002) for transduction
of progenitor and differentiated hematopoietic cells. Recently, a new LV carry-
ing the MV EnvGP on its surface was able to overcome vector restrictions in
both quiescent T and B cells (Frecha
et al
., 2008a, 2009). Importantly, naive as
well as memory T and B cells were efficiently transduced, while no apparent
activation, cell-cycle entry, or phenotypic switching were detected, opening the
door to a multitude of gene therapy and immunotherapy applications. Vectors
derived from HIV pseudotyped with Sendai virus fusion protein F (Kowolik and
Yee, 2002) or E1E2 from hepatitis C virus (Bartosch
et al
., 2003), and such
vectors are able to transduce human hepatoma cells and primary human hepa-
tocytes efficiently, although they are unable to enter nonliver cells. The GP64
glycoprotein from baculovirus
et al
multinuclear polyhedrosis
virus pseudotyped FIV efficiently and also showed excellent hepatocyte tropism
(Kang
Autographa californica
et al
., 2005).
B. Identification of viral cell entry receptors using pseudoparticles
The screening of cDNA libraries has emerged as a powerful tool to identify and
clone viral entry receptors. It is an alternative to the use of human/Chinese
hamster radiation hybrid panels of cells. In order to clone an unknown receptor
by complementation screens, cDNA from a cell permissive to infection by a
certain virus is introduced into a nonpermissive cell. As some recessive cell lines
are poorly transfectable, the use of pseudoparticles provides a good tool to
transduce the cDNA library for this cloning strategy. A retroviral cDNA library
approach, involving transfer and expression of cDNAs from highly infectable
cells to nonpermissive cells, has been used to clone and identify the MuLV
polytropic X-receptor (Battini
et al
., 1999; Tailor
et al
., 1999a; Yang
et al
., 1999),
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