Evidence for localization of biologically active recombinant retroviral vector to lymph nodes in mice injected intramuscularly.
We have developed a novel gene transfer drug, HIV-IT(V), for the treatment of HIV infection in humans. HIV-IT(V) is a retroviral vector encoding the HIV-1 IIIB env and rev genes and a neomycin resistance marker gene (neor). We have recently reported that HIV-IT(V) administered intramuscularly to male mice localizes primarily to the site of injection. In this study, we have investigated more extensively the localization and biological activity of HIV-IT(V) administered intramuscularly to female mice. Consistent with our previous findings, retroviral DNA was detected by PCR at the site of injection. Retroviral DNA was also detected in proximal lymph nodes, a tissue not examined previously. Potential for drainage of vector particles to regional lymph nodes was indicated by experiments showing that intramuscular injection of fluorescein-labeled latex beads concentrated in the regional lymph nodes in mice. The localization of retroviral DNA to the injection site and regional lymph nodes may play a role in the induction of the HIV-specific CTL responses detected in splenocyte populations isolated from mice 21 days after injection with HIV-IT(V).
Kamantigue
E
E
Viagène Inc., San Diego, CA 92121, USA.
Edwards
W
W
Chada
S
S
Brumm
D
D
Austin
M
M
Irwin
M
M
Mento
S
S
Kowal
K
K
Sajjadi
N
N
D000818:Animals; D001483:Base Sequence; D004274:DNA, Recombinant / Q000032:analysis; D004279:DNA, Viral / Q000032:analysis*; D005260:Female; D018014:Gene Transfer Techniques; D015752:Genes, env / Q000235:genetics; D005822:Genetic Vectors / Q000008:administration & dosage*; D015497:HIV-1 / Q000235:genetics* / Q000276:immunology; D007273:Injections, Intramuscular; D009052:Leukemia Virus, Murine / Q000235:genetics*; D008198:Lymph Nodes / Q000737:chemistry / Q000821:virology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D018482:Muscle, Skeletal / Q000737:chemistry; D016133:Polymerase Chain Reaction / Q000379:methods; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology
D004274:DNA, Recombinant; D004279:DNA, Viral