Partial inhibition of human immunodeficiency virus replication by type I interferons: impact of cell-to-cell viral transfer.
Type I interferons (IFN) inhibit several steps of the human immunodeficiency virus type 1 (HIV) replication cycle. Some HIV proteins, like Vif and Vpu, directly counteract IFN-induced restriction factors. Other mechanisms are expected to modulate the extent of IFN inhibition. Here, we studied the impact of IFN on various aspects of HIV replication in primary T lymphocytes. We confirm the potent effect of IFN on Gag p24 production in supernatants. Interestingly, IFN had a more limited effect on HIV spread, measured as the appearance of Gag-expressing cells. Primary isolates displayed similar differences in the inhibition of p24 release and virus spread. Virus emergence was the consequence of suboptimal inhibition of HIV replication and was not due to the selection of resistant variants. Cell-to-cell HIV transfer, a potent means of virus replication, was less sensitive to IFN than infection by cell-free virions. These results suggest that IFN are less active in cell cultures than initially thought. They help explain the incomplete protection by naturally secreted IFN during HIV infection and the unsatisfactory outcome of IFN treatment in HIV-infected patients.
Vendrame
Daniela
D
Institut Pasteur, Virus and Immunity Unit, CNRS URA 3015, 25-28 rue du Dr. Roux, 75724 Paris, France.
Sourisseau
Marion
M
Perrin
Virginie
V
Schwartz
Olivier
O
Mammano
Fabrizio
F
D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000821:virology; D002460:Cell Line; D002478:Cells, Cultured; D016655:HIV Core Protein p24 / Q000235:genetics / Q000378:metabolism; D015658:HIV Infections / Q000821:virology; D015497:HIV-1 / Q000187:drug effects* / Q000472:pathogenicity / Q000502:physiology*; D006801:Humans; D007370:Interferon Type I / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology*; D019169:Jurkat Cells; D013601:T-Lymphocytes / Q000166:cytology / Q000821:virology*; D014779:Virus Replication / Q000187:drug effects*
D016655:HIV Core Protein p24; D007370:Interferon Type I
Cell Host Microbe. 2008 Jun 12;3(6):388-98
18541215
J Virol. 2008 Jun;82(11):5145-52
18385227
J Interferon Cytokine Res. 2001 Oct;21(10):861-9
11710999
Clin Immunol. 2007 May;123(2):121-8
17112786
J Antimicrob Chemother. 2007 Mar;59(3):565-8
17213263
Cell Host Microbe. 2007 Sep 13;2(3):193-203
18005734
J Exp Med. 1989 Mar 1;169(3):1137-51
2466937
Antiviral Res. 1994 Jul;24(2-3):205-19
7526792
Nat Med. 1996 Mar;2(3):338-42
8612235
Lancet. 1988 Nov 26;2(8622):1214-7
2903953
AIDS. 1989 Feb;3(2):97-100
2496726
Proc Natl Acad Sci U S A. 1991 Apr 15;88(8):3195-9
2014240
Proc Natl Acad Sci U S A. 1989 Jul;86(13):4958-62
2472636
Virology. 1993 Mar;193(1):303-12
8438572
Cell Host Microbe. 2008 Apr 17;3(4):245-52
18342597
J Virol. 2007 Sep;81(18):10201-6
17609277
AIDS. 1995 Sep;9(9):1025-35
8527074
Biochimie. 1998 Aug-Sep;80(8-9):745-54
9865497
J Acquir Immune Defic Syndr Hum Retrovirol. 1997 Dec 1;16(4):247-53
9402071
J Virol. 2000 Dec;74(23):10882-91
11069982
Nat Med. 2008 Oct;14(10):1077-87
18806803
Proc Natl Acad Sci U S A. 2003 Apr 1;100(7):4144-9
12644702
Antiviral Res. 2006 Sep;71(2-3):117-21
16621040
Adv Cancer Res. 2008;101:249-76
19055946
Virology. 1994 Nov 1;204(2):823-7
7524241
Virology. 1995 Nov 10;213(2):413-24
7491766
AIDS Res Hum Retroviruses. 1987 Summer;3(2):125-33
3113463
Proc Natl Acad Sci U S A. 2006 Jan 31;103(5):1440-5
16434471
Clin Infect Dis. 2008 Jul 1;47(1):94-101
18513148
Science. 1989 May 5;244(4904):575-7
2470148
J Infect Dis. 1996 May;173(5):1107-14
8627061
J Virol. 1995 Dec;69(12):7699-711
7494279
J Virol. 2000 May;74(10):4505-11
10775586
Proc Natl Acad Sci U S A. 2003 Dec 9;100(25):15154-9
14657387
Virology. 2008 Mar 30;373(1):85-97
18082865
Lancet. 1988 Nov 26;2(8622):1218-22
2903954
J Virol. 1992 Mar;66(3):1321-8
1738192
PLoS Pathog. 2008 Feb 29;4(2):e1000007
18389079
Nat Rev Microbiol. 2008 Nov;6(11):815-26
18923409
J Infect Dis. 1992 May;165(5):793-8
1349031
AIDS. 1989 Jan;3(1):27-31
2496708
J Virol. 1992 Dec;66(12):7543-8
1279206
J Leukoc Biol. 2006 Nov;80(5):984-93
16916960
J Immunol. 1990 Oct 15;145(8):2669-76
1976701
Antimicrob Agents Chemother. 2000 Apr;44(4):920-8
10722492
Ann Intern Med. 1990 Jun 1;112(11):805-11
1971503
Virology. 1993 Mar;193(1):138-48
7679856
J Infect Dis. 1997 Sep;176(3):811-4
9291341
J Infect Dis. 1994 Jun;169(6):1351-5
7910838
Retrovirology. 2007 Jun 12;4:40
17565686
J Virol. 1991 Nov;65(11):6325-30
1920634
Nature. 2008 Jan 24;451(7177):425-30
18200009
J Interferon Res. 1986 Apr;6(2):143-52
2425014
J Virol. 2006 Aug;80(15):7645-57
16840343
Clin Immunol Immunopathol. 1990 Feb;54(2):200-19
1688522
Eur J Med Res. 2001 Dec 17;6(12):507-24
11772539
AIDS Res Hum Retroviruses. 1988 Aug;4(4):287-94
3144996
AIDS Res Hum Retroviruses. 1990 Aug;6(8):1045-9
2121192
Nat Med. 2008 Jun;14(6):641-7
18500349
Science. 1988 Sep 2;241(4870):1221-3
3261888
AIDS Rev. 2002 Jul-Sep;4(3):148-56
12416449
Virology. 1998 Aug 1;247(2):265-73
9705919
Virology. 1995 Dec 20;214(2):379-86
8553538
J Infect Dis. 1995 Apr;171(4):822-8
7706808
Nat Rev Drug Discov. 2007 Dec;6(12):975-90
18049472
Biotherapy. 1994;8(1):23-31
7547078
J Virol. 1998 Mar;72(3):2208-12
9499078
Nucleic Acids Res. 1989 Feb 11;17(3):969-78
2922280
J Virol. 2007 Jan;81(2):1000-12
17079292
Antimicrob Agents Chemother. 1991 Jan;35(1):62-7
1707604
Lancet. 1985 Mar 16;1(8429):602-4
2857946
J Virol. 1999 Jan;73(1):290-6
9847332