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Role of CCR5Δ32 mutation in protecting patients with Schistosoma mansoni infection against hepatitis C viral infection or progression

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Abstract

Schistosomiasis has been incriminated in the significant increase in hepatitis C virus (HCV) infections, although the association has not been adequately explained. We hypothesized that the CCR5Δ32 mutation may be involved in the high prevalence of HCV with schistosomiasis. The aim was to explore the association between the CCR5Δ32 mutation in schistosomiasis patients and protection against HCV infection or progression. We compared 220 schistosomiasis patients (S group) and 190 patients with HCV and schistosomiasis (HCV/S group) for the presence of the CCR5Δ32 mutation. Clinical, biochemical, and radiological assessments were done. HCV infection was diagnosed with anti-HCV antibodies and a recombinant HCV antigen-based rapid immunochromatographic test, and confirmed by HCV reverse transcriptase PCR. HCV genotyping was done by reverse hybridization line probe assay. Schistosomiasis was diagnosed by FAST-ELISA and indirect hemagglutination for Schistosoma mansoni antibodies, and stool analysis for ova. Polymorphisms of the CCR5 receptor gene were assessed by PCR-based genotyping of the 32-bp deletion at the CCR5 locus in whole blood. Of HCV/S patients, 91.6 vs. 91.8 % of S patients had CCR5 WT/WT homozygosity (nonmutants). Heterozygous and homozygous CCR5Δ32 mutation patterns (CCR5Δ32/WT and CCR5Δ32/Δ32) were distributed similarly in the HCV/S and S groups (6.8 vs. 7.2 % and 0.53 vs. 0.90 %, respectively; p > 0.05, OR = 0.97). Genotype 4 was the predominant viral genotype (93 % of cases). No differences were observed in CCR5 gene patterns according to viral genotype, viral RNA count, or ALT level. However, CCR5Δ32 mutants (homozygous and heterozygous) had a lower rate of severe hepatic fibrosis vs. nonmutants (27 vs. 42 %, p = 0.101, OR = 0.51). Moreover, 53.4 % of CCR5Δ32/WT mutants showed spontaneous viral clearance vs. 26.2 % of nonmutants (p = 0.000, OR = 4.1). In conclusion, no association was detected between the CCR5Δ32 mutation and HCV disease susceptibility in schistosomiasis patients. However, patients with the CCR5Δ32 mutation and HCV infection were less prone to severe hepatic fibrosis and more likely to have spontaneous viral clearance than patients with the nonmutant genotype.

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References

  • Abdallahi OM, Hanna S, Reggi MD, Gharib B (1999) Visualization of oxygen radical production in mouse liver in response to infection with Schistosoma mansoni. Liver 19:495–500

    Article  PubMed  CAS  Google Scholar 

  • Abdel-Wahab MF, Esmat G, Milad M, Abdel-Razek S, Strickland GT (1989) Characteristic sonographic pattern of schistosomal hepatic fibrosis. Am J Trop Med Hyg 40:72–76

    PubMed  CAS  Google Scholar 

  • Ahlenstiel G, Woitas RP, Rockstroh J, Spengler U (2004) CC-chemokine receptor 5 (CCR5) in hepatitis C—at the crossroads of the antiviral immune response? J Antimicrob Chemother 53:895–898

    Article  PubMed  CAS  Google Scholar 

  • Albadalejo J, Alonso R, Antionozzi R, Bogard M, Bourgault AM, Colucci G, Fenner T, Petersen H, Sala E, Vincelette J, Young C (1998) Multicenter evaluation of the COBAS AMPLICOR HCV assay, an integrated PCR system for rapid detection of hepatitis C virus RNA in the diagnostic laboratory. J Clin Microbiol 36(4):862–865

    PubMed  CAS  Google Scholar 

  • Ansel KM, Mc Heyzer-Willaims LJ, Ngo VN, McHeyzer-Williams MG, Cyster JG (1999) In vivo activated CD4T cells upregulate CXC chemokine receptor 5 and reprogramme their response to lymphoid chemokines. J Exp Med 190:123–1134

    Article  Google Scholar 

  • Bahgat MM, El-Far MA, Mesalam AA, Ismaeil AA, Ibrahim AA, Gewaid HE, Maghraby AS, Ali MA, Abdel-Shafy DN (2010) Schistosoma mansoni soluble egg antigens enhance HCV replication in mammalian cells. J Infect Dev Ctries 4(4):226–234

    Article  PubMed  CAS  Google Scholar 

  • Barakat R, Farghaly A, El Morshedy H, Hassan M, Miller W (1998) Impact of National Schistosomiasis Control Program in Kafr El-Sheikh governorate, Nile Delta, Egypt: an independent evaluation. J Egypt Public Health Assoc 73:737–753

    PubMed  CAS  Google Scholar 

  • Barber Y, Rubio C, Fernandez E, Rubio M, Fibla J (2001) Host genetic background at CCR5 chemokine receptor and vitamin D receptor loci and human immunodeficiency virus (HIV) type 1 disease progression among HIV-seropositive injection drug users. J Infect Dis 184:1279–1288

    Article  PubMed  CAS  Google Scholar 

  • Belnoue E, Kayibanda M, Deschemin JC, Viguier M, Mack M, Kuziel WA, Renia L (2003) CCR5 deficiency decreases susceptibility to experimental cerebral malaria. Blood 101:4253–4259

    Article  PubMed  CAS  Google Scholar 

  • Bichler KH, Feil G, Zumbragel A, Eipper E, Dyballa S (2001) Schistosomiasis: a critical review. Curr Opin Urol 11:97–101

    Article  PubMed  CAS  Google Scholar 

  • Cook DN, Beck MA, Coffman TM, Kirby SL, Sheridan JF, Pragnell IB, Smithies O (1995) Requirement of MIP1a for an inflammatory response to viral infection. Science 269:1583–1585

    Article  PubMed  CAS  Google Scholar 

  • De Clercq E, Schols D (2001) Inhibition of HIV infection by CXCR4 and CCR5 chemokine receptor antagonists. Antivir Chem Chemother 12:19–31

    PubMed  Google Scholar 

  • 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 381:667–673

    Article  PubMed  CAS  Google Scholar 

  • El-Gaafary MM, Rekacewicz C, Abdel-Rahman AG, Allam MF, Hosseiny ME, Hamid MA, Colombani F, Sultan Y, El-Aidy S, Fontanet A, Mohamed MK (2005) Surveillance of acute hepatitis C in Cairo. Egypt J Med Virol 76:520–525

    Article  Google Scholar 

  • El-Kady IM, El-Masry SA, Badra G, Halafawy KA (2004a) Different cytokine patterns in patients coinfected with hepatitis C virus and Schistosoma mansoni. Egypt J Immunol 1:23–29

    Google Scholar 

  • El-Kady IM, Lotfy M, Badray G, El-Masry S, Wakedy I (2004b) Interleukin (IL)-4, IL 10, IL-18 and IFN-γ cytokines pattern in patients with combined hepatitis C virus and Schistosoma mansoni infections. Scand J Immunol 61:87–91

    Article  Google Scholar 

  • El-Khoby T, Galal N, Fenwick A, Barakat R, El-Hawey A, Nooman Z, Habib M, Dewolfe Miller F (2000) The epidemiology of schistosomiasis in Egypt: summary findings in nine governorates. Am J Trop Med Hyg 62:88–99

    PubMed  CAS  Google Scholar 

  • El-Rooby A (1985) Management of hepatic schistosomiasis. Semin Liver Dis 5:263–276

    Article  PubMed  CAS  Google Scholar 

  • El-Sahn AA, El-Masry AG, Shehata AI, Ibrahim HF (2002) Current status of S. mansoni infection in El-Prince village, Alexandria Governorate. J Egypt Public Health Assoc 77:537–552

    PubMed  Google Scholar 

  • Garred P, Madsen HO, Petersen J, Marquart H, Hansen TM, Freiesleben Sorensen S, Volck B, Svejgaard A, Andersen V (1998) Chemokine receptor 5 polymorphism in rheumatoid arthritis. J Rheumatol 25:1462–1465

    PubMed  CAS  Google Scholar 

  • Garson JA, Tuke PW, Ring C, Tedder RS (1990) Enhanced detection by PCR of hepatitis C virus RNA. Lancet 336:878–879

    Article  PubMed  CAS  Google Scholar 

  • Glass WG, Liu MT, Kuziel WA, Lane TE (2001) Reduced macrophage infiltration and demyelination in mice lacking the chemokine receptor CCR5 following infection with a neurotropic coronavirus. Virology 288:8–17

    Article  PubMed  CAS  Google Scholar 

  • Gomez-Reino JJ, Pablos JL, Carreira PE, Santiago B, Serrano L, Vicario JL, Balsa A, Figueroa M, de Juan MD (1999) Association of rheumatoid arthritis with a functional chemokine receptor, CCR5. Arthritis Rheum 42:989–992

    Article  PubMed  CAS  Google Scholar 

  • Goulding C, Murphy A, MacDonald G, Barrett S, Crowe J, Hegarty J, McKiernan S, Kelleher D (2005) The CCR5-D32 mutation: impact on disease outcome in individuals with hepatitis C infection from a single source. Gut 54:1157–1161

    Article  PubMed  CAS  Google Scholar 

  • Goyal A, Suneeth PV, Kumar GT, Shukla DK, Arora N, Sarin SK (2006) CCR5Δ32 mutation does not influence the susceptibility to HCV infection, severity of liver disease and response to therapy in patients with chronic hepatitis C. World J Gastroenterol 12(29):4721–4726

    PubMed  CAS  Google Scholar 

  • Hellier S, Frodsham AJ, Hennig BJ, Klenerman P, Knapp S, Ramaley P, Satsangi J, Wright M, Zhang L, Thomas HC, Thursz M, Hill AV (2003) Association of genetic variants of the chemokine receptor CCR5 and its ligands, RANTES and MCP-2, with outcome of HCV infection. Hepatology 38:1468–1476

    PubMed  CAS  Google Scholar 

  • Husain S, Goila R, Shahi S, Banerjea A (1998) First report of a healthy Indian heterozygous for delta 32 mutant of HIV-1 coreceptor-CCR5 gene. Gene 207:141–147

    Article  PubMed  CAS  Google Scholar 

  • Lalani AS (1999) Use of chemokine receptors by poxviruses. Science 286(5446):1968–1971

    Article  PubMed  CAS  Google Scholar 

  • Lehman EM, Wilson ML (2009) Epidemic hepatitis C virus infection in Egypt: estimates of past incidence and future morbidity and mortality. J Viral Hepat 16:650–658

    Article  PubMed  CAS  Google Scholar 

  • Madwar MA, El Tahawy M, Strichland GT (1989) Relationship between uncomplicated schistosomiasis and hepatitis B infection. Trans R Soc Trop Med Hyg 83:233–236

    Article  PubMed  CAS  Google Scholar 

  • Martin K, Heinzlmann M, Borchers R, Mack M, Loeschke K, Folwaczny C (2001) Delta 32 mutation of the chemokine-receptor 5 gene in inflammatory bowel disease. Clin Immunol 98:18–22

    Article  PubMed  CAS  Google Scholar 

  • Nansen A, Christensen JP, Andreasen SO, Bartholdy C, Christensen JE, Thomsen AR (2002) The role of CC chemokine receptor 5 in antiviral immunity. Blood 99:1237–1245

    Article  PubMed  CAS  Google Scholar 

  • Promrat K, McDermott DH, Gonzalez CM, Kleiner DE, Koziol DE, Lessie M, Merrell M, Soza A, Heller T, Ghany M, Park Y, Alter HJ, Hoofnagle JH, Murphy PM, Liang TJ (2003) Associations of chemokine system polymorphisms with clinical outcomes and treatment responses of chronic hepatitis C. Gastroenterology 124:352–360

    Article  PubMed  CAS  Google Scholar 

  • Ross AG, Bartley PB, Sleigh AC, Olds GR, Li Y, Williams GM, McManus DP (2002) Schistosomiasis. N Engl J Med 346:1212–1220

    Article  PubMed  Google Scholar 

  • Sato N, Kuziel WA, Melby PC, Reddick RL, Kostecki V, Zhao W, Maeda N, Ahuia SK, Ahuia SS (1999) Defects in the generation of IFN-c are overcome to control infection with Leishmania donovani in CC chemokine receptor (CCR) 5-, macrophage inflammatory protein-1 alpha-, in CCR2-deficient mice. J Immunol 163:5519–5525

    PubMed  CAS  Google Scholar 

  • Strizki JM, Xu S, Wagner NE, Wojcik L, Liu J, Hou Y, Endres M, Palani A, Shapiro S, Clader JW, Greenlee WJ, Tagat JR, McCombie S, Cox K, Fawzi AB, Chou CC, Pugliese-Sivo C, Davies L, Moreno ME, Ho DD, Trkola A, Stoddart CA, Moore JP, Reyes GR, Baroudy BM (2001) SCH-C (SCH 351125), an orally bioavailable, small molecule antagonist of the chemokine receptor CCR5, is a potent inhibitor of HIV-1 infection in vitro and in vivo. Proc Natl Acad Sci U S A 98:12718–12723

    Article  PubMed  CAS  Google Scholar 

  • Stuyver L, Rossau R, Wyseur A, Duhamel M, Vanderborght B, Heuverswyn HV, Maertens G (1993) Typing of hepatitis C virus isolates and characterization of new subtypes using a line probe assay. J Gen Virol 74:1093–1102

    Article  PubMed  CAS  Google Scholar 

  • Tsang VC, Tsang KR, Hancock K, Kelly MA, Wilson BC, Maddison SE (1983) Schistosoma mansoni adult microsomal antigens, a serologic reagent. 1. Systematic fractionation, quantitation and characterization of antigenic components. J Immunol 130:1359–1365

    PubMed  CAS  Google Scholar 

  • WHO-World Health Organization (1991) Proposal for a practical guide to the standardized use of ultrasound in the assessment of pathological changes. In Meeting on ultrasonography in schistosomiasis, TDR/SCH/Ultrason, Cairo, Egypt, pp. 32

  • Woitas RP, Ahlenstiel G, Iwan A, Rockstroh JK, Brackmann HH, Kupfer B, Matz B, Offergeld R, Sauerbruch T, Spengler U (2002) Frequency of the HIV-protective CC chemokine receptor 5-Delta32/Delta32 genotype is increased in hepatitis C. Gastroenterology 122:1721–1728

    Article  PubMed  CAS  Google Scholar 

  • Zhou Y, Kurihara T, Ryseck RP, Yang Y, Ryan C, Loy J, Warr G, Bravo R (1998) Impaired macrophage function and enhanced T cell-dependent immune response in mice lacking CCR5, the mouse homologue of the major HIV-1 coreceptor. J Immunol 160:4018–4025

    PubMed  CAS  Google Scholar 

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Acknowledgments

We thank K. Shashok (AuthorAID in the Eastern Mediterranean) for improving the use of the English language in the manuscript.

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Authors and Affiliations

  1. Department of Parasitology, Faculty of Medicine, Suez Canal University, 4.5 Km region, Ismailia, 41522, Egypt

    Amal Abdul-rasheed El-Moamly

  2. Department of Microbiology and Immunology, Faculty of Medicine, Suez Canal University, Ismailia, Egypt

    Mohamed Aly El-Sweify

  3. Department of Parasitology, Faculty of Medicine, Al-Azhar University, Cairo, Egypt

    Rafiaa M. Rashad

  4. Department of Clinical Pathology, Faculty of Medicine, Suez Canal University, Ismailia, Egypt

    Esam M. Abdalla

  5. Department of Internal Medicine, Faculty of Medicine, Suez Canal University, Ismailia, Egypt

    Mostafa M. Ragheb & Mohamed M. Awad

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  1. Amal Abdul-rasheed El-Moamly
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  2. Mohamed Aly El-Sweify
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  3. Rafiaa M. Rashad
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Correspondence to Amal Abdul-rasheed El-Moamly.

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El-Moamly, A.Ar., El-Sweify, M.A., Rashad, R.M. et al. Role of CCR5Δ32 mutation in protecting patients with Schistosoma mansoni infection against hepatitis C viral infection or progression. Parasitol Res 112, 2745–2752 (2013). https://doi.org/10.1007/s00436-013-3380-9

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  • DOI: https://doi.org/10.1007/s00436-013-3380-9

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