MLV-derived retroviral vectors selective for CD4-expressing cells and resistant to neutralization by sera from HIV-infected patients

Retroviral vectors derived from amphotropic murine leukemia viruses (MLV) m ediate gene transfer into almost all human cells and are thus not suitable for in vivo applications in gene therapy in which cell-specific gene delive ry is required. We and others recently reported the generation of MLV-deriv ed vectors pseudotyped by variants of the envelope glycoproteins (Env) of h uman immunodeficiency virus type 1 (HIV-1), thus displaying the CD4-depende nt tropism of the parental lentivirus (Mammano et al., 1997, J. Virol. 71, 3341-3345; Schnierle et al, 1997, Proc. Natl. Acad. Sci. USA 76, 8640-8645) . However, because of their HIV-l-derived envelopes these vectors are neutr alized by HIV-specific antibodies present in some infected patients. To cir cumvent this problem, we pseudotyped MLV capsid particles with variants of Env proteins derived from the apathogenic simian immunodeficiency virus (SI Vagm) of African green monkeys (AGM; Chlorocebus pygerythrus). Truncation o f the C-terminal domain of the transmembrane protein was found to be necess ary to allow formation of infectious pseudotype vectors. These [MLV(SIVagm) ] vectors efficiently transduced various human CD4-expressing cell lines us ing the coreceptors CCR5 and Bonzo to enter target cells. Moreover, they we re resistant to neutralization by antibodies directed against HIV-1. Theref ore, [MLV(SIVagm)] vectors will be useful to study the mechanisms of SIVagm cell entry and for the selective gene transfer into CD4+ T-cells of AIDS p atients. (C) 2000 Academic Press.