Aberrant, noninfectious HIV-1 particles are released by chronically infected human T cells transduced with a retroviral vector expressing an interfering HIV-1 variant.
The expression of the nonproducer F12-HIV-1 genome has been previously shown to protect the host cell from HIV superinfection. In order to estimate the efficacy of the F12-HIV genome as an anti-HIV reagent also in cells already infected, an HIV-1 chronically infected Hut-78 cell clone (D10) was superinfected with an amphotropic mouse/human pseudotype retrovirus whose genome expresses both the F12-HIV genome and the selection marker gene (i.e. the c-DNA of a truncated form of the nerve growth factor receptor, NGFr) under the control of F12-HIV 5'LTR. D10 cells homogenously expressing the F12-HIV genome (T-D10) released unaltered amounts of retrovirions whose infectivity was, however, dramatically impaired (from 9 x 10(3) in D10 to < 10(0.5). TCID50/ml in T-D10 supernatants). Electron microscopy showed that the morphology of retrovirions released by T-D10 cells was heavily altered, both in size and shape. Furthermore, no retrotranscription products were detectable in CD4 cells challenged with T-D10 retrovirions. For the first time, the block in the infectivity of HIV released from already infected cells through the expression of an anti-HIV retroviral vector was demonstrated. These data could have important implications both from a perspective of F12-HIV-based anti-HIV gene therapy and, in general, on the role that nonproducer and/or defective HIV could play 'in vivo' in HIV infection and AIDS pathogenesis.
Bona
R
R
Laboratory of Virology, Istituto Superiore di Sanità, Rome, Italy.
d'Aloja
P
P
Olivetta
E
E
Modesti
A
A
Modica
A
A
Geraci
A
A
Ferrari
G
G
Verani
P
P
Federico
M
M
D018929:Cell Culture Techniques; D002908:Chronic Disease; D015316:Genetic Therapy; D005822:Genetic Vectors; D016679:Genome, Viral; D015658:HIV Infections / Q000235:genetics*; D015497:HIV-1 / Q000235:genetics*; D006801:Humans; D012190:Retroviridae / Q000235:genetics; D015163:Superinfection / Q000235:genetics; D013601:T-Lymphocytes / Q000821:virology*; D014762:Viral Interference / Q000235:genetics*; D014771:Virion / Q000472:pathogenicity / Q000648:ultrastructure