A Novel Lentivirus Vector Derived from Apathogenic Simian Immunodeficiency Virus

Abstract

The improvement of gene transfer efficiency in growth-arrested cells using human immunodeficiency virus type 1 (HIV-1)-derived vectors led to the development of vectors derived from other members of the lentivirus family. Here we report the generation of a lentiviral vector derived from the apathogenic molecular virus clone SIVagm3mc of the simian immunodeficiency virus from African green monkeys (Cercocebus pygerythrus). Upon pseudotyping with the G-protein of vesicular stomatitis virus (VSV-G), the SIVagm-derived vector was shown to transduce proliferating and growth-arrested mammalian cell lines, including human cells. After in vivo inoculation into the striatum of the adult rat brain, the vector was shown to transduce terminally differentiated neurons and oligodendrocytes as well as quiescent and reactive astrocytes. Moreover, SIVagm transfer vector mRNA was efficiently packaged by HIV-1 vector particles. Homologous [SIV(SIV)] vectors generated by using the SIVagm-derived envelope glycoproteins allowed selective gene transfer into human CD4(+)/CCR5(+) cells. Thus, the SIVagm3mc-derived vector is a useful alternative to HIV-1-derived lentiviral vectors in somatic gene therapy.

Gene therapy progress and prospects: Novel gene therapy approaches for AIDS

“…The SIVbased vector, pseudotyped with its own envelope (homologous SIV(SIV)) was able to selectively transduce human CD4(+)/CCR5(+) cells. 10 Nonprimate retroviral vectors, like the feline immunodeficiency virus (FIV)-based vectors have also been developed. [11][12][13] Importantly, although the virus used in delivery may vary (HIV, SIV, or FIV), the main objective of such approaches is the same.…”

Shuttle of lentiviral vectors via transplanted cells in vivo

“…Lentiviral vectors, usually derived from HIV or alternatively from non-human primate lentiviruses, are able to efficiently infect nondividing cells in vitro and in vivo, based on a nuclear import mechanism of the host cell (eg, Naldini et al, 1 Zennou et al, 2 Fleury et al 3 and Stitz et al 4 ). Stable gene transfer and expression in a broad variety of cells have been obtained via direct viral vector injection without any immune response or loss of expression efficacy.…”

“…Stable gene transfer and expression in a broad variety of cells have been obtained via direct viral vector injection without any immune response or loss of expression efficacy. [4][5][6] An increasing number of studies report efficient ex vivo gene transfer into cells prior to transplantation, for example, transduction of haematopoietic stem cells with subsequent repopularization of irradiated NOD/SCID mice bone marrow 7 or CNS cells. 8 Furthermore, lentiviral ex vivo gene transfer is not only performed for therapeutic gene transfer but also to label cells with suitable reporter genes, such as enhanced green fluorescent protein (eGFP), for example, to explore differentiation of stem or progenitor cells after cell transplantation or co-cultivation with other cell types.…”

Cell Culture Processes for the Production of Viral Vectors for Gene Therapy Purposes

“…The extensive body of knowledge that has been generated on this virus has allowed researchers to reengineer it as a gene vector. HIV-1 remains the best studied vector (Lever et al 2004), although recent work has revealed the potential of HIV-2 (Sadaie et al 1998) SIV (Schnell et al 2000;Stitz et al 2001), EIAV (equine infectious anemia virus) (Olsen 1998;Mitrophanous et al 1999;Ikeda et al 2003) 2002; Loewen et al 2003) and BIV (bovine immunodeficiency virus) (Takahashi et al 2002) as vectors.…”