CAF-mediated human immunodeficiency virus (HIV) type 1 transcriptional inhibition is distinct from α-defensin-1 HIV inhibition

TLY Chang, F François, A Mosoian… - Journal of virology, 2003 - Am Soc Microbiol
TLY Chang, F François, A Mosoian, ME Klotman
Journal of virology, 2003Am Soc Microbiol
ABSTRACT CD8+ T lymphocytes can inhibit human immunodeficiency virus type 1 (HIV-1)
replication by secreting a soluble factor (s) known as CD8+ T-lymphocyte antiviral factor
(CAF). One site of CAF action is inhibition of HIV-1 RNA transcription, particularly at the step
of long terminal repeat (LTR)-driven gene expression. The inhibitory effect of CAF on HIV-1
LTR activation is mediated through STAT1 activation. A recent study reports that α-defensins
1 to 3 account for CAF activity against HIV-1. Here, we address whether α-defensins …
Abstract
CD8+ T lymphocytes can inhibit human immunodeficiency virus type 1 (HIV-1) replication by secreting a soluble factor(s) known as CD8+ T-lymphocyte antiviral factor (CAF). One site of CAF action is inhibition of HIV-1 RNA transcription, particularly at the step of long terminal repeat (LTR)-driven gene expression. The inhibitory effect of CAF on HIV-1 LTR activation is mediated through STAT1 activation. A recent study reports that α-defensins 1 to 3 account for CAF activity against HIV-1. Here, we address whether α-defensins, particularly α-defensin-1, contribute to CAF-mediated inhibition of HIV-1 transcription. Both recombinant α-defensin-1 and CAF derived from herpesvirus saimiri (HVS)-transformed CD8+ cells inhibited HIV-1 infection and gene expression. For both factors, the inhibition of HIV-1 infection did not occur at the level of viral entry. Pretreatment of cells with α-defensin-1 followed by a washing out prior to infection blocked infection by HIV-1, indicating that direct inactivation of virions was not required for its inhibitory effect. In contrast to CAF, α-defensin-1 did not inhibit phorbol myristate acetate- or Tat-mediated HIV-1 LTR activation in a transient transfection system, nor did it activate STAT1 tyrosine phosphorylation. Furthermore, α-defensins 1 to 3 were below the level of detection in a panel of HVS-transformed CD8+ cells with potent HIV-1 inhibitory activity and a neutralizing antibody against α-defensins 1 to 3 did not reverse the inhibitory effect of CAF on HIV-1 gene expression in infected cells and on HIV-1 LTR activation in transfected cells. Taken together, our results suggest that α-defensin-1 inhibits HIV-1 infection following viral entry but that α-defensins 1 to 3 are not responsible for the HIV-1 transcriptional inhibition by CAF.
American Society for Microbiology