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A p r i l 2 2 - 2 3 , 2 0 1 9
A t h e n s , G r e e c e
Page 69
Archives of Clinical Microbiology
ISSN: 1989-8436
Virology and Infectious Diseases 2019
EuroSciCon Conference on
Virology and Infectious Diseases
H
IV-1 expresses several accessory proteins to counteract host anti-viral restriction factors to facilitate viral replication
and disease progression. One such protein, Vpr, has been implicated in affecting multiple cellular processes, but
its mechanism remains elusive. Here we report that Vpr targets TET2 for polyubiquitylation by the VprBP-DDB1-CUL4-
ROC1 E3 ligase and subsequent degradation. Genetic inactivation or Vpr-mediated degradation of TET2 enhances HIV-
1 replication and substantially sustained expression of the pro-inflammatory cytokine interleukin-6 (IL-6), correlated
with reduced recruitment of histone deacetylase 1 and 2 to and enhanced histone H3 acetylation of the IL-6 promoter
during resolution phase. Blocking IL-6 signaling reduced the ability of Vpr to enhance HIV-1 replication. We conclude
that HIV-1 Vpr degrades TET2 to sustain IL-6 expression to enhance viral replication and disease progression. These
results suggest disrupting the Vpr-TET2-IL6 axis may prove clinically beneficial to reduce both viral replication and
inflammation during HIV-1 infection.
lsu@med.unc.eduHIV-1 Vpr targets TET2 for degradation by
CRL4VprBP E3 ligase to sustain IL-6 expression and
enhance HIV-1 pathogenesis
Lishan Su
University of North Carolina, USA
Arch Clin Microbiol 2019, Volume:10
DOI: 10.4172/1989-8436-C1-018