DNA-encoding enzymatically active HIV-1 reverse transcriptase, but not the inactive mutant, confers resistance to experimental HIV-1 challenge.
The present study was undertaken to examine the immunogenicity of a single plasmid DNA representing the reverse transcriptase (RT) of HIV-1. Plasmids containing the enzymatically active RT as well as a mutated nonenzymatically active RT with nucleotide (nt)-binding motifs of YMDD and YMLL, respectively, were used to immunize mice. Both constructs induced similar good antibody and T cell responses, with a tendency towards antibody directed to peptides representing the active and mutated sites. Immunized mice were challenged with a murine pseudotype HIV-1/MuLV infected spleen cells. Seven out of 10 mice immunized with RT had no recoverable HIV-1, while 10 individuals immunized with the RT mutant and all the 18 controls had high levels of recoverable HIV-1. This indicates that mutation of RT reduces the desired immunogenicity.
Isaguliants
M G
MG
D.I. Ivanovsky Institute of Virology, Moscow, Russia.
Petrakova
N N
NN
Zuber
B
B
Pokrovskaya
K
K
Gizatullin
R
R
Kostyuk
D A
DA
Kjerrström
A
A
Winberg
G
G
Kochetkov
S N
SN
Hinkula
J
J
Wahren
B
B
D016915:AIDS Vaccines / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D000595:Amino Acid Sequence; D000818:Animals; D002478:Cells, Cultured; D004195:Disease Models, Animal; D015658:HIV Infections / Q000517:prevention & control*; D054303:HIV Reverse Transcriptase / Q000235:genetics* / Q000276:immunology* / Q000378:metabolism; D015497:HIV-1 / Q000276:immunology; D006801:Humans; D007114:Immunization; D007963:Leukocytes, Mononuclear; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D009154:Mutation; D010455:Peptides / Q000138:chemical synthesis; D019444:Vaccines, DNA / Q000008:administration & dosage / Q000276:immunology*
D016915:AIDS Vaccines; D010455:Peptides; D019444:Vaccines, DNA; D054303:HIV Reverse Transcriptase