Pathogenic prion protein fragment (PrP106-126) promotes human immunodeficiency virus type-1 infection in peripheral blood monocyte-derived macrophages.

Abstract:

:Transfusion of blood and blood products contaminated with the pathogenic form of prion protein Prp(sc), thought to be the causative agent of variant a Creutzfeldt-Jakob disease (vCJD), may result in serious consequences in recipients with a compromised immune system, for example, as seen in HIV-1 infection. In the present study, we demonstrate that treatment of peripheral blood monocyte-derived macrophages (MDM) with PrP106-126, a synthetic domain of PrP(sc) that has intrinsic functional activities related to the full-length protein, markedly increased their susceptibility to HIV-1 infection, induced cytokine secretion, and enhanced their migratory behavior in response to N-formyl-l-methionyl-l-leucyl-l-phenylalanine (fMLP). Live-cell imaging of MDM cultured in the presence of PrP106-126 showed large cell clusters indicative of cellular activation. Tyrosine kinase inhibitor STI-571, protein kinase C inhibitor K252B, and cyclin-dependent kinase inhibitor olomoucine attenuated PrP106-126-induced altered MDM functions. These findings delineate a previously undefined functional role of PrP106-126-mediated host cell response in promoting HIV-1 pathogenesis.

journal_name

Virology

journal_title

Virology

authors

Bacot SM,Feldman GM,Yamada KM,Dhawan S

doi

10.1016/j.virol.2014.11.032

subject

Has Abstract

pub_date

2015-02-01 00:00:00

pages

372-376

eissn

0042-6822

issn

1096-0341

pii

S0042-6822(14)00571-6

journal_volume

476

pub_type

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