CD8+ T cell-mediated CXC chemokine receptor 4-simian/human immunodeficiency virus suppression in dually infected rhesus macaques - PubMed (original) (raw)
CD8+ T cell-mediated CXC chemokine receptor 4-simian/human immunodeficiency virus suppression in dually infected rhesus macaques
Janet M Harouse et al. Proc Natl Acad Sci U S A. 2003.
Abstract
We coinfected rhesus macaques with CXC chemokine receptor 4- and CC chemokine receptor 5-specific simian/human immunodeficiency viruses (SHIVs) to elucidate the basis for the early dominance of R5-tropic strains seen in HIV-infected humans. We found no intrinsic barrier to the transmission and dissemination of high-dose X4-SHIV in the dually infected macaques. In animals that maintained a viral set point, the R5 virus predominated. The time of appearance of R5 dominance coincided with the development of virus-specific immunity (3-6 weeks postinfection), suggestive of differential immune control of the two viruses. Indeed, after depletion of CD8+ T cells in the coinfected animals, X4 virus emerged, supporting the concept that differential CD8+ T cell-mediated immune control of X4- and R5-SHIV replication is responsible for the selective outgrowth of R5 viruses. These findings provide critical insights into a key question related to HIV pathogenesis and have important implications for the development and testing of antiviral vaccines and therapeutics.
Figures
Fig. 1.
Viral replication, T cell subsets, and viral genotype in i.v. dually infected macaques. (i) Peripheral blood was collected in EDTA at designated time intervals and separated into plasma and cellular components. The absolute copies of viral RNA per ml of plasma (viremia, thick line) were determined by branched-DNA analysis (Bayer Diagnostics). The absolute number of CD3+CD4+ (▴) or CD3+CD8+(▵) cells per μl of blood as determined by Tru-Count FACS analysis. +, time that macaques were killed due to development of clinical symptoms of SAIDS. (ii) Percentage of CCR5- (•) or CXCR4- (○) specific env clones amplified by RT-PCR from plasma.
Fig. 2.
Virologic, immunologic, and genotypic measurements in IVAG dually infected macaques. The symbols are as described for Fig. 1. *, Presence of recombinant virus.
Fig. 3.
Changes in genotype of replicating virus after CD8+ T cell depletion in dually infected macaques. AJ12 was administered the mAb cM-T807 on days 0, 3, and 7 (arrows). Viral load and T cell subsets (i) and viral genotype (ii) were analyzed as described for Fig. 1.
Fig. 4.
Dominance of R5-SHIVSF162P3 after i.v. inoculation of macaques. The symbols are as described for Fig. 1.
Fig. 5.
X4-SHIVSF33A emerged in i.v. dual-infected macaques after CD8+ T cell depletion. Viral load and T cell subsets (i) and viral genotypes (ii) were determined as described for Fig. 1. The arrows indicate time of administration of the anti-CD8 mAb cM-T807.
Similar articles
- V3 loop-determined coreceptor preference dictates the dynamics of CD4+-T-cell loss in simian-human immunodeficiency virus-infected macaques.
Ho SH, Shek L, Gettie A, Blanchard J, Cheng-Mayer C. Ho SH, et al. J Virol. 2005 Oct;79(19):12296-303. doi: 10.1128/JVI.79.19.12296-12303.2005. J Virol. 2005. PMID: 16160156 Free PMC article. - Coreceptor switch in R5-tropic simian/human immunodeficiency virus-infected macaques.
Ho SH, Tasca S, Shek L, Li A, Gettie A, Blanchard J, Boden D, Cheng-Mayer C. Ho SH, et al. J Virol. 2007 Aug;81(16):8621-33. doi: 10.1128/JVI.00759-07. Epub 2007 May 30. J Virol. 2007. PMID: 17537860 Free PMC article. - Induction of CD8+ cells able to suppress CCR5-tropic simian immunodeficiency virus SIVmac239 replication by controlled infection of CXCR4-tropic simian-human immunodeficiency virus in vaccinated rhesus macaques.
Tsukamoto T, Yuasa M, Yamamoto H, Kawada M, Takeda A, Igarashi H, Matano T. Tsukamoto T, et al. J Virol. 2007 Nov;81(21):11640-9. doi: 10.1128/JVI.01475-07. Epub 2007 Aug 29. J Virol. 2007. PMID: 17728225 Free PMC article. - Coreceptor switch in infection of nonhuman primates.
Cheng-Mayer C, Tasca S, Ho SH. Cheng-Mayer C, et al. Curr HIV Res. 2009 Jan;7(1):30-8. doi: 10.2174/157016209787048500. Curr HIV Res. 2009. PMID: 19149552 Review.
Cited by
- Characterization of a CXCR4 antagonist TIQ-15 with dual tropic HIV entry inhibition properties.
Zhou Z, Guo J, Hetrick B, Tiwari S, Haikerwal A, Han Y, Bond VC, Huang MB, Mankowski MK, Snyder BA, Hogan PA, Sharma SK, Liotta DC, Reid TE, Wilson LJ, Wu Y. Zhou Z, et al. PLoS Pathog. 2024 Aug 15;20(8):e1012448. doi: 10.1371/journal.ppat.1012448. eCollection 2024 Aug. PLoS Pathog. 2024. PMID: 39146384 Free PMC article. - Spermine and spermidine bind CXCR4 and inhibit CXCR4- but not CCR5-tropic HIV-1 infection.
Harms M, Smith N, Han M, Groß R, von Maltitz P, Stürzel C, Ruiz-Blanco YB, Almeida-Hernández Y, Rodriguez-Alfonso A, Cathelin D, Caspar B, Tahar B, Sayettat S, Bekaddour N, Vanshylla K, Kleipass F, Wiese S, Ständker L, Klein F, Lagane B, Boonen A, Schols D, Benichou S, Sanchez-Garcia E, Herbeuval JP, Münch J. Harms M, et al. Sci Adv. 2023 Jul 7;9(27):eadf8251. doi: 10.1126/sciadv.adf8251. Epub 2023 Jul 5. Sci Adv. 2023. PMID: 37406129 Free PMC article. - [CCR5 antagonists and HIV-1 infection: Bases and consequences of this therapeutic approach].
Psomas KC, Corbeau P, Reynes J. Psomas KC, et al. Antibiotiques (Paris). 2010 Mar;12(1):27-41. doi: 10.1016/j.antib.2010.01.006. Epub 2010 Feb 18. Antibiotiques (Paris). 2010. PMID: 32288525 Free PMC article. French. - Pace of Coreceptor Tropism Switch in HIV-1-Infected Individuals after Recent Infection.
Arif MS, Hunter J, Léda AR, Zukurov JPL, Samer S, Camargo M, Galinskas J, Kallás EG, Komninakis SV, Janini LM, Sucupira MC, Diaz RS. Arif MS, et al. J Virol. 2017 Sep 12;91(19):e00793-17. doi: 10.1128/JVI.00793-17. Print 2017 Oct 1. J Virol. 2017. PMID: 28659473 Free PMC article. - Characterization of founder viruses in very early SIV rectal transmission.
Yuan Z, Ma F, Demers AJ, Wang D, Xu J, Lewis MG, Li Q. Yuan Z, et al. Virology. 2017 Feb;502:97-105. doi: 10.1016/j.virol.2016.12.018. Epub 2016 Dec 25. Virology. 2017. PMID: 28027479 Free PMC article.
References
- Fauci, A. S. (1996) Nature 384, 529–534. - PubMed
- Koot, M., Keet, I. P., Vos, A. H., de Goede, R. E., Roos, M. T., Coutinho, R. A., Miedema, F., Schellekens, P. T. & Tersmette, M. (1993) Ann. Intern. Med. 118, 681–688. - PubMed
- Cheng-Mayer, C., Seto, D., Tateno, M. & Levy, J. A. (1988) Science 240, 80–82. - PubMed
Publication types
MeSH terms
Substances
Grants and funding
- AI46980/AI/NIAID NIH HHS/United States
- R24RR16001/RR/NCRR NIH HHS/United States
- P51 RR000164/RR/NCRR NIH HHS/United States
- R24 RR016001/RR/NCRR NIH HHS/United States
- RR00164/RR/NCRR NIH HHS/United States
- R01 AI046980/AI/NIAID NIH HHS/United States
LinkOut - more resources
Full Text Sources
Research Materials