Inhibition of Human Immunodeficiency Virus Type 1 Infectivity by Secretory Leukocyte Protease Inhibitor Occurs Prior to Viral Reverse Transcription (original) (raw)
Infection of monocytes with human immunodeficiency virus the C-terminal domain contains the protease inhibiting retype 1 Ba-L (HIV-1 Ba-L) is significantly inhibited by treatment gion. However, when tested independently, neither domain with the serine protease inhibitor, secretory leukocyte protehad potent anti-HIV-1 activity. SLPI binding neither prease inhibitor (SLPI). SLPI does not appear to act on virus vented virus binding to monocytes nor attenuated the infecdirectly, but rather the inhibitory activity is most likely due tivity of any virus progeny that escaped inhibition by SLPI. to interaction with the host cell. The current study was initi-A polymerase chain reaction (PCR)-based assay for newly ated to investigate how SLPI interacts with monocytes to generated viral DNA demonstrated that SLPI blocks at or inhibit infection. SLPI was found to bind to monocytes with before viral DNA synthesis. Therefore, it most likely inhibits high affinity to a single class of receptor sites (Ò7,000 recepa step of viral infection that occurs after virus binding but tors per monocyte, K D ! 3.6 nmol/L). The putative SLPI rebefore reverse transcription. Taken together, the unique ceptor was identified as a surface protein with a molecular antiviral activity of SLPI, which may be independent of its weight of 55 Ô 5 kD. A well-characterized function of SLPI previously characterized antiprotease activity, appears to reis inhibition of neutrophil elastase and cathepsin G. Howside in disruption of the viral infection process soon after ever, two SLPI mutants (or muteins) that contain single virus binding. amino acid substitutions and exhibit greatly reduced prote-This is a US government work. There are no restrictions on ase inhibitory activity still bound to monocytes and retained its use. anti-HIV-1 activity. SLPI consists of two domains, of which
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