TY - JOUR
T1 - Inhibition of HIV-1 particle assembly by 2′,3′-cyclic- nucleotide 3′-Phosphodiesterase
AU - Wilson, Sam J.
AU - Schoggins, John W.
AU - Zang, Trinity
AU - Kutluay, Sebla B.
AU - Jouvenet, Nolwenn
AU - Alim, Mudathir A.
AU - Bitzegeio, Julia
AU - Rice, Charles M.
AU - Bieniasz, Paul D.
N1 - Funding Information:
We thank Rob Gifford, Marc Johnson, Beatrice Hahn, Stuart Neil, Theodora Hatziioannou, Masahiro Yamashita, Eric Poeschla, and Valgerdur Andrésdóttir for reagents and Kunihiro Uryo from the Rockefeller University Microscopy Resource Center and Henrik Molina at the Rockefeller University Proteomics Resource Center for technical assistance. This work was supported by NIH grants (R37AI064003 and R01AI50111) to P.D.B.
PY - 2012/10/18
Y1 - 2012/10/18
N2 - The expression of hundreds of interferon-stimulated genes (ISGs) causes the cellular "antiviral state" in which the replication of many viruses, including HIV-1, is attenuated. We conducted a screen for ISGs that inhibit HIV-1 virion production and found that 2′,3′-cyclic-nucleotide 3′-phosphodiesterase (CNP), a membrane-associated protein with unknown function in mammals has this property. CNP binds to the structural protein Gag and blocks HIV-1 particle assembly after Gag and viral RNA have associated with the plasma membrane. Several primate lentiviruses are CNP-sensitive, and CNP sensitivity/resistance is determined by a single, naturally dimorphic, codon (E/K40) in the matrix domain of Gag. Like other antiretroviral proteins, CNP displays interspecies variation in antiviral activity. Mice encode an inactive CNP variant and a single amino acid difference in murine versus human CNP determines Gag binding and antiviral activity. Some cell types express high levels of CNP and we speculate that CNP evolved to restrict lentivirus replication therein.
AB - The expression of hundreds of interferon-stimulated genes (ISGs) causes the cellular "antiviral state" in which the replication of many viruses, including HIV-1, is attenuated. We conducted a screen for ISGs that inhibit HIV-1 virion production and found that 2′,3′-cyclic-nucleotide 3′-phosphodiesterase (CNP), a membrane-associated protein with unknown function in mammals has this property. CNP binds to the structural protein Gag and blocks HIV-1 particle assembly after Gag and viral RNA have associated with the plasma membrane. Several primate lentiviruses are CNP-sensitive, and CNP sensitivity/resistance is determined by a single, naturally dimorphic, codon (E/K40) in the matrix domain of Gag. Like other antiretroviral proteins, CNP displays interspecies variation in antiviral activity. Mice encode an inactive CNP variant and a single amino acid difference in murine versus human CNP determines Gag binding and antiviral activity. Some cell types express high levels of CNP and we speculate that CNP evolved to restrict lentivirus replication therein.
UR - http://www.scopus.com/inward/record.url?scp=84867645688&partnerID=8YFLogxK
U2 - 10.1016/j.chom.2012.08.012
DO - 10.1016/j.chom.2012.08.012
M3 - Article
C2 - 23084924
AN - SCOPUS:84867645688
VL - 12
SP - 585
EP - 597
JO - Cell Host and Microbe
JF - Cell Host and Microbe
SN - 1931-3128
IS - 4
ER -