Abstract
We set up a cohort of HIV-infected, asymptomatic Japanese patients with hemophilia for follow-up study in 1995. All subjects who had been infected with HIV-1 for more than 10 years met the criteria for long-term nonprogressors (LTNPs) at the time of entry; however, some of them later developed lymphopenia and required antiretroviral treatment during five more years of observation. In this study, we investigated the impacts of the CCL3L1 dose on the long-term prognosis in the subjects with chronic HIV-1 infection. We collected genomic DNA from 95 long-term survivors including 48 nonprogressors and 47 subjects receiving antiretroviral treatment. The distributions of CCL3L1 copy number significantly differed between the 95 HIV-1-infected subjects with hemophilia and 205 controls. Average copy number of CCL3L1 in the HIV-1-infected subjects was significantly lower than in control (5.00 ± 0.22 vs 3.35 ± 0.24, p < 0.001). Moreover, the subjects possessing two or less copies of CCL3L1 had significantly higher risk of acquiring HIV-1. However, CCL3L1 copy number variations had no significant effect on the disease progression among the LTNP subjects who had been afflicted with chronic HIV-1 infection for more than 15 years, when compared between nonprogressors and patients under treatment (3.68 ± 0.37 vs 3.02 ± 0.29, ns). Furthermore, variations in the CCL3L1 copy number had little effect on the levels of HIV-1 load among them. We conclude that variation in the CCL3L1 copy number is apparently not a factor that determines the prognosis of chronic HIV-1 infection, even though it is linked to HIV-1 susceptibility.
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References
CDC (1992) 1993 Revised classification system for HIV infection and expanded surveillance case definition for AIDS among adolescents and adults. MMWR 41(no. RR-17)
Dragic T, Litwin V, Allaway GP, Martin SR, Huang Y, Nagashima KA, Cayanan C, Maddon PJ, Koup RA, Moore JP, Paxton WA (1996) HIV-1 entry into CD4+cells is mediated by the chemokine receptor CC-CKR-5. Nature 381(6584):667–673
Gonzalez E, Kulkarni H, Bolivar H, Mangano A, Sanchez R, Catano G, Nibbs RJ, Freedman BI, Quinones MP, Bamshad MJ, Murthy KK, Rovin BH, Bradley W, Clark RA, Anderson SA, O, connell RJ, Agan BK, Ahuja SS, Bologna R, Sen L, Dolan MJ, Ahuja SK (2005) The influence of CCL3L1 gene-containing segmental duplications on HIV-1/AIDS susceptibility. Science 307(5714):1434–1440
Henrard DR, Phillips JF, Muenz LR, Blattner WA, Wiesner D, Eyster ME, Goedert JJ (1995) Natural history of HIV-1 cell-free viremia. JAMA 274(7):554–558
Hirashima M, Ono T, Nakao M, Nishi H, Kimura A, Nomiyama H, Hamada F, Yoshida MC, Shimada K (1992) Nucleotide sequence of the third cytokine LD78 gene and mapping of all three LD78 gene loci to human chromosome 17. DNA Seq 3(4):203–212
Ho DD, Neumann AU, Perelson AS, Chen W, Leonard JM, Markowitz M (1995) Rapid turnover of plasma virions and CD4 lymphocytes in HIV-1 infection. Nature 373(6510):123–126
Hogan CM, Hammer SM (2001) Host determinants in HIV infection and disease. Part 2: genetic factors and implications for antiretroviral therapeutics. Ann Intern Med 134(10):978–996
Ioannidis JP, Rosenberg PS, Goedert JJ, Ashton LJ, Benfield TL, Buchbinder SP, Coutinho RA, Eugen-Olsen J, Gallart T, Katzenstein TL, Kostrikis LG, Kuipers H, Louie LG, Mallal SA, Margolick JB, Martinez OP, Meyer L, Michael NL, Operskalski E, Pantaleo G, Rizzardi GP, Schuitemaker H, Sheppard HW, Stewart GJ, Theodorou ID, Ullum H, Vicenzi E, Vlahov D, Wilkinson D, Workman C, Zagury JF, O’Brien TR (2001) Effects of CCR5-Delta32, CCR2–64I, and SDF-1 3′A alleles on HIV-1 disease progression: an international meta-analysis of individual-patient data. Ann Intern Med 135(9):782–795
McDermott DH, Zimmerman PA, Guignard F, Kleeberger CA, Leitman SF, Murphy PM (1998) CCR5 promoter polymorphism and HIV-1 disease progression. Multicenter AIDS Cohort Study (MACS). Lancet 352(9131):866–870
Mellors JW, Munoz A, Giorgi JV, Margolick JB, Tassoni CJ, Gupta P, Kingsley LA, Todd JA, Saah AJ, Detels R, Phair JP, Rinaldo CR Jr (1997) Plasma viral load and CD4+lymphocytes as prognostic markers of HIV-1 infection. Ann Intern Med 126(12):946–954
Menten P, Wuyts A, Van Damme J (2002) Macrophage inflammatory protein-1. Cytokine Growth Factor Rev 13(6):455–481
Munkanta M, Terunuma H, Takahashi M, Hanabusa H, Miura T, Ikeda S, Sakai M, Fujii T, Takahashi Y, Oka S, Matsuda J, Ishikawa M, Taki M, Takashima Y, Mimaya J, Ito M, Kimura A, Yasunami M (2005) HLA-B polymorphism in Japanese HIV-1-infected long-term surviving hemophiliacs. Viral Immunol 18(3):500–505
Muñoz A, Kirby AJ, He YD, Margolick JB, Visscher BR, Rinaldo CR, Kaslow RA, Phair JP (1995) Long-term survivors with HIV-1 infection: Incubation period and longitudinal patterns of CD4+lymphocytes. J Acquir Immune Defic Syndr Human Retrovirol 8(5):496–505
Pantaleo G, Menzo S, Vaccarezza M, Graziosi C, Cohen OJ, Demarest JF, Montefiori D, Orenstein JM, Fox C, Schrager LK, Margolick JB, Buchbinder S, Giorgi JV, Fauci AS (1995) Studies in subjects with long-term nonprogressive human immunodeficiency virus infection. N Engl J Med 332(4):209–216
Shao W, Tang J, Song W, Wang C, Li Y, Wilson CM, Kaslow RA (2007) CCL3L1 and CCL4L1: variable gene copy number in adolescents with and without human immunodeficiency virus type 1 (HIV-1) infection. Genes Immun 8(3):224–231
Townson JR, Barcellos LF, Nibbs RJ (2002) Gene copy number regulates the production of the human chemokine CCL3-L1. Eur J Immunol 32(10):3016–3026
UNAIDS (2006) 2006 Report on the global HIV/AIDS epidemic. Geneva: Joint United Nations Program on HIV/AIDS
Wei X, Ghosh SK, Taylor ME, Johnson VA, Emini EA, Deutsch P, Lifson JD, Bonhoeffer S, Nowak MA, Hahn BH, Saag MS, Shaw GM (1995) Viral dynamics in human immunodeficiency virus type 1 infection. Nature 373(6510):117–122
Acknowledgements
We are grateful for samples of HIV-1-positive patients to Drs. H. Hanabusa (Ogikubo Hospital), J. Matsuda (Teikyo University School of Medicine), M. Sakai (University of Occupational and Environmental Health), S. Ikeda (Sasebo Municipal Hospital), and T. Fujii (Hiroshima University School of Medicine). This work was supported in part by research grants from the Ministry of Health, Labor and Welfare, Japan, the Japan Health Science Foundation, and the program of Founding Research Centers for Emerging and Reemerging Infection Disease supported by the Ministry of Education, Culture, Sports, Science, and Technology, Japan.
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Nakajima, T., Ohtani, H., Naruse, T. et al. Copy number variations of CCL3L1 and long-term prognosis of HIV-1 infection in asymptomatic HIV-infected Japanese with hemophilia. Immunogenetics 59, 793–798 (2007). https://doi.org/10.1007/s00251-007-0252-4
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DOI: https://doi.org/10.1007/s00251-007-0252-4