HIV-1 Antiviral Activity of Recombinant Natural Killer Cell Enhancing Factors, NKEF-A and NKEF-B, Members of the Peroxiredoxin Family

Ralf Geiben-Lynn,Mischo Kursar,Nancy V Brown,Marylyn M Addo,Hungyi Shau,Judy Lieberman,Andrew D Luster,Bruce D Walker

doi:10.1074/jbc.m209964200

Ralf Geiben-Lynn, Mischo Kursar + Show 6 more

Open Access

https://doi.org/10.1074/jbc.m209964200

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Abstract

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.

Highlights

CD8ϩ T-cells inhibit HIV-11 replication by both cytolytic and non-cytolytic mechanisms [1]
These results indicate that the peroxiredoxin family members natural killer cell enhancing factors (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
We show that recombinant NKEF-A and NKEF-B protein exogenously added to HIV-1 cultures can inhibit HIV-1 replication and that T-cells transfected with NKEF-A or NKEF-B cDNA were resistant to HIV-1 infection

Summary

Introduction

CD8ϩ T-cells inhibit HIV-11 replication by both cytolytic and non-cytolytic mechanisms [1]. 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. Chemokines (MIP-1␣, MIP-1␤, and regulated on activation normal T-cell expressed and secreted (RANTES)) produced by CD8ϩ T-cells have been shown to inhibit HIV-1 replication in vitro [11, 12] at the level of viral entry [13, 14] and may play a critical role in vivo as an antiviral host defense [15, 16].

Results

Conclusion