Type I interferon is a powerful inhibitor of in vivo HIV-1 infection and preserves human CD4(+) T cells from virus-induced depletion in SCID mice transplanted with human cells
C. Lapenta et al., Type I interferon is a powerful inhibitor of in vivo HIV-1 infection and preserves human CD4(+) T cells from virus-induced depletion in SCID mice transplanted with human cells, VIROLOGY, 263(1), 1999, pp. 78-88
Although several studies are available on the in vitro inhibitory activitie
s of type I interferon (IFN) on HIV-1 replication, the role of these cytoki
nes in the pathogenesis of AIDS is still matter of conjecture. Both benefic
ial and adverse effects have been envisaged and considered as a possible ra
tionale for the development of either IFN or adi-IFN therapies in HIV-1-inf
ected patients. In the present study, we have evaluated the efficacy of hum
an type I IFN on HIV-1 infection and virus-induced depletion of human CD4 T
cells in two models established in SCID mice. In SCID mice transplanted wi
th human U937 cells (U937-SCID mouse model), continuous treatment with type
I consensus IFN (CIFN) resulted in a total suppression of HIV-1 infection.
This inhibitory effect was superior to that obtained after AZT treatments.
Results from an ensemble of experiments in SCID mice transplanted with eit
her control or genetically modified human U937 cells transduced with a Tat-
inducible IFN-alpha gene (LTR-IFN-A2 U937) indicated that low levels of IFN
-alpha, produced locally as a result of virus infection, were extremely eff
ective in inhibiting acute HIV infection and virus replication. Of interest
, LTR-IFN-A2 U937 cells conferred a strong anti-HIV-1 protection to coinjec
ted bystander U937 cells. Notably, experiments with SCID mice reconstituted
with human PBL (hu-PBL-SCID mouse model) showed that treatment with CIFN i
nhibited HIV-1 replication more effectively than AZT treatment. Remarkably,
treatment with CIFN resulted in a clear-cut protection from the virus-indu
ced depletion of human CD4 T cells, which was also associated with the gene
ration of an antibody response toward HIV-1 antigens in 50% of the virus-in
jected xenografts. These results suggest that type I IFN efficiently preser
ves human CD4(+) cells from virus-induced damage in hu-PBL-SCID mice, not o
nly by inducing an antiviral state in target cells but also by stimulating
anti-HIV-1 human immune responses in vivo. (C) 1999 Academic Press.