Biology Reference
In-Depth Information
Figure 19.4. E¨ect of HIV-1 infection on CD4 T cell levels. Hu-PBL-SCID mice were challenged
with SF-2, SF-162, and chimeric recombinant viruses exhibiting reciprocal substitutions of the env
gene on the backbone of parental SF-2 and SF-162 genomes. env-SF-162 indicates the recombinant
SF-2 virus carrying the SF-162 env region, whereas env-SF-2 indicates the recombinant SF-162
virus carrying the SF-2 env region. Xenochimeras were challenged with the di¨erent viral strains
at 2 h or 2 wks after engraftment and sacri®ced 4 wks later.
consistent with the acquisition of a memory phenotype by CEM cells during
their growth in SCID mice ( Lapenta et al., 1998).
TESTING OF ANTIVIRAL SUBSTANCES AND STRATEGIES
Any substance, before its clinical use, has to be tested in an animal model, in
which drug bioavailability, metabolism, clearance, toxicity, and antiviral e½-
cacy can be studied. Although hu-PBL-SCID mice proved to be valuable tools
for investigating some aspects of human immunode®ciency virus ( HIV ) infec-
tion and AIDS pathogenesis, their current use for antiviral screening has been
hampered by two major limitations: i) the restriction of HIV-1 infection to a
limited number of human cells, resulting in poor levels of viremia; and ii) the
relatively short time of persistence of virus infection. In this regard, human cell
lines grafted into SCID mice may o¨er new opportunities for the preclinical
testing of antiviral drugs and therapeutic strategies, especially because of their
practical advantages and potential implementation. We recently reported that
di¨erent lymphoblastoid and monocytoid cell lines can be injected into SCID
mice to support HIV-1 infection. Anti-mouse a/b IFN or anti-PMN antibody
treatment can be performed to enhance tumor growth, resulting in a high level
of engraftment. HIV-1 infection of the graft results in multiple virus replication
