TY - JOUR
T1 - Infectivity enhancement by HIV-1 Nef is dependent on the pathway of virus entry
T2 - Implications for HIV-based gene transfer systems
AU - Luo, Tianci
AU - Douglas, Janet L.
AU - Livingston, Robyn L.
AU - Garcia, J. Victor
N1 - Funding Information:
We thank N. Landau for the amphotropic MLV envelope expression construct obtained through the AIDS Research and Reference Reagent Program, M. Emerman for the HeLa-MAGI cells, and J. Rose for the VSV-G clone. We also thank J. Foster and E. O’Neill for their comments on the manuscript. This work was supported by grants Al-33331 and Al-39416 (J.V.G.), by Cancer Center Support (CORE) Grant CA-21765 from the National Cancer Institute, and by the American Lebanese Syrian Associated Charities (ALSAC) of St. Jude Children’s Research Hospital. T.L. and J.D. are supported by individual postdoctoral NRSA Training Grants F32 AI-09591 and F32 CA-74581 from the National Institute of Allergy and Infectious Diseases and the National Cancer Institute.
PY - 1998/2/15
Y1 - 1998/2/15
N2 - Retroviruses have been extensively used in the development of gene transfer systems. Recently, there has been a great deal of interest in the use of lentiviruses for gene transfer because they infect nondividing cells. Human immunodeficiency virus (HIV) has been the lentivirus most often used for this purpose, but its genomic complexity and limited tropism present some challenges to the establishment of efficient gene transfer systems. In this paper we present data showing intrinsic differences between the infectivity of wild-type HIV and HIV particles pseudotyped with heterologous envelope glycoproteins. Interestingly, HIV pseudotypes with envelope glycoproteins from the amphotropic murine leukemia virus or the vesicular stomatitis virus (VSV) are 3 and 40 times more infectious than wild-type HIV, respectively. In addition, we show that the reliance on Nef expression for maximal infectivity of HIV particles is dependent on the path of virus entry. The dependence on Nef for higher infectivity is greater for amphotropic pseudotypes and wild- type HIV than for VSV-G pseudotypes. We conclude that VSV-G pseudotypes of HIV vectors are an excellent choice for gene transfer purposes and Nef- mediated vital infectivity enhancement is affected by virus entry pathway.
AB - Retroviruses have been extensively used in the development of gene transfer systems. Recently, there has been a great deal of interest in the use of lentiviruses for gene transfer because they infect nondividing cells. Human immunodeficiency virus (HIV) has been the lentivirus most often used for this purpose, but its genomic complexity and limited tropism present some challenges to the establishment of efficient gene transfer systems. In this paper we present data showing intrinsic differences between the infectivity of wild-type HIV and HIV particles pseudotyped with heterologous envelope glycoproteins. Interestingly, HIV pseudotypes with envelope glycoproteins from the amphotropic murine leukemia virus or the vesicular stomatitis virus (VSV) are 3 and 40 times more infectious than wild-type HIV, respectively. In addition, we show that the reliance on Nef expression for maximal infectivity of HIV particles is dependent on the path of virus entry. The dependence on Nef for higher infectivity is greater for amphotropic pseudotypes and wild- type HIV than for VSV-G pseudotypes. We conclude that VSV-G pseudotypes of HIV vectors are an excellent choice for gene transfer purposes and Nef- mediated vital infectivity enhancement is affected by virus entry pathway.
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U2 - 10.1006/viro.1997.8966
DO - 10.1006/viro.1997.8966
M3 - Article
C2 - 9499797
AN - SCOPUS:0032520144
VL - 241
SP - 224
EP - 233
JO - Virology
JF - Virology
SN - 0042-6822
IS - 2
ER -