Item request has been placed!
×
Item request cannot be made.
×
Processing Request
Proviruses with identical sequences comprise a large fraction of the replication-competent HIV reservoir.
Item request has been placed!
×
Item request cannot be made.
×
Processing Request
- Additional Information
- Source:
Publisher: Public Library of Science Country of Publication: United States NLM ID: 101238921 Publication Model: eCollection Cited Medium: Internet ISSN: 1553-7374 (Electronic) Linking ISSN: 15537366 NLM ISO Abbreviation: PLoS Pathog Subsets: MEDLINE
- Publication Information:
Original Publication: San Francisco, CA : Public Library of Science, c2005-
- Subject Terms:
- Abstract:
The major obstacle to curing HIV infection is the persistence of cells with intact proviruses that can produce replication-competent virus. This HIV reservoir is believed to exist primarily in CD4+ T-cells and is stable despite years of suppressive antiretroviral therapy. A potential mechanism for HIV persistence is clonal expansion of infected cells, but how often such clones carry replication-competent proviruses has been controversial. Here, we used single-genome sequencing to probe for identical HIV sequence matches among viruses recovered in different viral outgrowth cultures and between the sequences of outgrowth viruses and proviral or intracellular HIV RNA sequences in uncultured blood mononuclear cells from eight donors on suppressive ART with diverse proviral populations. All eight donors had viral outgrowth virus that was fully susceptible to their current ART drug regimen. Six of eight donors studied had identical near full-length HIV RNA sequences recovered from different viral outgrowth cultures, and one of the two remaining donors had identical partial viral sequence matches between outgrowth virus and intracellular HIV RNA. These findings provide evidence that clonal expansion of HIV-infected cells is an important mechanism of reservoir persistence that should be targeted to cure HIV infection.
- References:
Nat Med. 2009 Aug;15(8):893-900. (PMID: 19543283)
J Virol. 1995 Aug;69(8):5087-94. (PMID: 7541846)
Nat Med. 2003 Jun;9(6):727-8. (PMID: 12754504)
J Exp Med. 2009 Jun 8;206(6):1273-89. (PMID: 19487424)
Science. 1988 Nov 25;242(4882):1171-3. (PMID: 2460925)
Proc Natl Acad Sci U S A. 2008 Oct 28;105(43):16725-30. (PMID: 18936487)
PLoS Pathog. 2016 Aug 05;12(8):e1005689. (PMID: 27494508)
Nat Med. 1999 May;5(5):512-7. (PMID: 10229227)
Nat Biotechnol. 2007 Dec;25(12):1407-10. (PMID: 18066037)
Methods Mol Biol. 2005;304:3-15. (PMID: 16061962)
J Virol. 2015 Nov 18;90(3):1369-76. (PMID: 26581989)
J Virol. 2013 Sep;87(18):10313-23. (PMID: 23678164)
Science. 1996 Mar 15;271(5255):1582-6. (PMID: 8599114)
Cell. 2013 Oct 24;155(3):540-51. (PMID: 24243014)
J Clin Microbiol. 2014 Nov;52(11):3944-51. (PMID: 25187636)
Bioinformatics. 2000 Apr;16(4):400-1. (PMID: 10869039)
Nature. 1997 May 8;387(6629):183-8. (PMID: 9144289)
Prog Nucleic Acid Res Mol Biol. 2002;71:91-147. (PMID: 12102562)
J Virol. 1999 Jan;73(1):152-60. (PMID: 9847317)
Science. 1997 Nov 14;278(5341):1291-5. (PMID: 9360926)
J Clin Microbiol. 2005 Jan;43(1):406-13. (PMID: 15635002)
Retrovirology. 2015 Nov 11;12:93. (PMID: 26559632)
PLoS Pathog. 2014 Mar 20;10(3):e1004010. (PMID: 24651464)
Science. 1995 Jan 27;267(5197):483-9. (PMID: 7824947)
J Infect Dis. 2010 Jan 15;201(2):293-6. (PMID: 20001856)
Cell. 2015 Jan 29;160(3):420-32. (PMID: 25635456)
AIDS. 2008 Feb 19;22(4):497-501. (PMID: 18301062)
PLoS Pathog. 2017 Feb 22;13(2):e1006230. (PMID: 28225830)
J Virol. 2006 Jul;80(13):6441-57. (PMID: 16775332)
Science. 1997 Nov 14;278(5341):1295-300. (PMID: 9360927)
Science. 2014 Aug 1;345(6196):570-3. (PMID: 25011556)
Nat Med. 2016 Sep;22(9):1043-9. (PMID: 27500724)
Proc Natl Acad Sci U S A. 2014 May 13;111(19):7078-83. (PMID: 24706775)
Proc Natl Acad Sci U S A. 2016 Feb 16;113(7):1883-8. (PMID: 26858442)
J Clin Microbiol. 2016 Apr;54(4):902-11. (PMID: 26763968)
Open Forum Infect Dis. 2015 Aug 26;2(4):ofv123. (PMID: 26478893)
Science. 1988 Nov 25;242(4882):1168-71. (PMID: 2460924)
J Virol. 2005 Aug;79(15):9625-34. (PMID: 16014925)
Proc Natl Acad Sci U S A. 2016 Dec 6;113(49):E7908-E7916. (PMID: 27872306)
J Virol. 2001 Jul;75(14):6508-16. (PMID: 11413318)
Proc Natl Acad Sci U S A. 2009 Jun 9;106(23):9403-8. (PMID: 19470482)
Science. 2014 Jul 11;345(6193):179-83. (PMID: 24968937)
PLoS Pathog. 2013 Feb;9(2):e1003174. (PMID: 23459007)
Clin Infect Dis. 2010 Mar 15;50(6):912-9. (PMID: 20156060)
Clin Infect Dis. 2006 Jun 1;42(11):1608-18. (PMID: 16652319)
- Grant Information:
HHSN261200800001C United States CA NCI NIH HHS; HHSN261200800001E United States CA NCI NIH HHS
- Accession Number:
0 (Anti-HIV Agents)
- Publication Date:
Date Created: 20170323 Date Completed: 20170803 Latest Revision: 20240716
- Publication Date:
20250114
- Accession Number:
PMC5378418
- Accession Number:
10.1371/journal.ppat.1006283
- Accession Number:
28328934
No Comments.