HIV-1 antiviral activity of recombinant natural killer cell enhancing factors, NKEF-A and NKEF-B, members of the peroxiredoxin family.
CD8(+) T-cells are a major source for the production of non-cytolytic factors that inhibit HIV-1 replication. In order to characterize further these factors, we analyzed gene expression profiles of activated CD8(+) T-cells using a human cDNA expression array containing 588 human cDNAs. mRNA for the chemokine I-309 (CCL1), the cytokines granulocyte-macrophage colony-stimulating factor and interleukin-13, and natural killer cell enhancing factors (NKEF) -A and -B were up-regulated in bulk CD8(+) T-cells from HIV-1 seropositive individuals compared with seronegative individuals. Recombinant NKEF-A and NKEF-B inhibited HIV-1 replication when exogenously added to acutely infected T-cells at an ID(50) (dose inhibiting HIV-1 replication by 50%) of approximately 130 nm (3 microg/ml). Additionally, inhibition against dual-tropic simian immunodeficiency virus and dual-tropic simian-human immunodeficiency virus was found. T-cells transfected with NKEF-A or NKEF-B cDNA were able to inhibit 80-98% HIV-1 replication in vitro. Elevated plasma levels of both NKEF-A and NKEF-B proteins were detected in 23% of HIV-infected non-treated individuals but not in persons treated with highly active antiviral therapy or uninfected persons. These results indicate that the peroxiredoxin family members NKEF-A and NKEF-B are up-regulated in activated CD8(+) T-cells in HIV infection, and suggest that these antioxidant proteins contribute to the antiviral activity of CD8(+) T-cells.
Geiben-Lynn
Ralf
R
Partners AIDS Research Center, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02129, USA. acceleration@rcn.com
Kursar
Mischo
M
Brown
Nancy V
NV
Addo
Marylyn M
MM
Shau
Hungyi
H
Lieberman
Judy
J
Luster
Andrew D
AD
Walker
Bruce D
BD
D001798:Blood Proteins / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology*; D018414:CD8-Positive T-Lymphocytes / Q000378:metabolism; D015870:Gene Expression; D015497:HIV-1 / Q000187:drug effects* / Q000502:physiology; D006360:Heat-Shock Proteins; D006801:Humans; D019169:Jurkat Cells; D007694:Killer Cells, Natural / Q000187:drug effects* / Q000276:immunology; D010544:Peroxidases; D054464:Peroxiredoxins; D011994:Recombinant Proteins / Q000097:blood / Q000235:genetics / Q000494:pharmacology; D014162:Transfection; D014779:Virus Replication / Q000187:drug effects
D001798:Blood Proteins; D006360:Heat-Shock Proteins; D011994:Recombinant Proteins; D010544:Peroxidases; C086065:PRDX2 protein, human; D054464:Peroxiredoxins