ROLE OF CYTOTOXIC T LYMPHOCYTE IN ADENOVIRUS INFECTION
Downloads
The successful development of adenovirus vectors for vaccines and gene therapy will require a better understanding of the host immune response. Using the ELISPOT assay to measure IFN-g-secreting CD8þ cells, we identify immunodominant epitopes of the adenovirus hexon and DNA-binding protein in BALB/c and C57BL/6 mice. The T-cell response to the intramuscular administration of adenovirus serotype 5 peaks within a few weeks and gradually declines but is still detectable after 12 weeks. A second administration did not substantially increase the number of reactive T cells. The CD8þ T-cell response was also similar between wild type and E1-deleted adenovirus. When B-cell-deficient mice were injected with adenovirus encoding the gene for secreted alkaline phosphatase, sera phosphatase activity was reduced more quickly in mice pre-exposed to adenovirus. These results add to the evidence that cell-mediated immunity is a substantial barrier to therapeutic adenoviral vectors and provide more quantitative tools to measure cellular immune responses to adenovirus.
Berger J et al. Secreted placental alkaline phosphatase: a powerful new quantitative
Chapman B, Thayer R, Vincent K, Haigwood N. Effect of intron A from human
cytomegalovirus (Towne) immediate-early gene on heterologous expression in mammalian cells. Nucleic Acids Res 1991; 19: 3979–3986.
Chakrabarti, S., Mautner, V., Osman, H., Collingham, K.E., Fegan, C.D., Klapper,
P.E., Moss, P.A. & Milligan, D.W. (2002) Adenovirus infections following allogeneic stem cell transplantation: incidence and outcome in relation to graft manipulation, immunosuppress-sion, and immune recovery. Blood, 100, 1619–1627.
Callan, M.F., Steven, N., Krausa, P., Wilson, J.D., Moss, P.A., Gillespie, G.M., Bell, J.I.,
Rickinson, A.B. & McMichael, A.J. (1996) Large clonal expansions of CD8+ T cells in acute infectious mononucle- osis. Nature Medicine, 2, 906–911.
Callan, M.F., Tan, L., Annels, N., Ogg, G.S., Wilson, J.D., O’Callaghan, C.A., Steven, N., McMichael, A.J. & Rickinson, A.B. (1998a) direct visualization of antigen-specific CD8+ T cells during the primary immune response to Epstein–Barr virus in vivo. Journal of Experi- mental Medicine, 187, 1395–1402.
-Catamo, E.; Zupin, L.; Freato, N.; Polesello, V.; Celsi, F.; Crocè, S.L.; Masutti, F.; Pozzato, G.; Segat, L.; Crovella, S. HLA-G regulatory polymorphisms are associated with susceptibility to HCV infection. HLA 2017, 89, 135–142.
Chakrabarti, S., Mautner, V., Osman, H., Collingham, K.E., Fegan, C.D., Klapper, P.E., Moss, P.A. & Milligan, D.W. (2002) Adenovirus infections following allogeneic stem cell transplantation: incidence and outcome in relation to graft manipulation, immunosuppres- sion, and immune recovery. Blood, 100, 1619–1627.
Coutinho, A.E.; Chapman, K.E. The anti-inflammatory and immunosuppressive effects of glucocorticoids, and mechanistic insights. Mol. Cell. Endocrinol. 2011, 335, 2-13. [CrossRef] [PubMed]
de Wit, J.; Borghans, J.A.; Kesmir, C.; van Baarle, D. Editorial: Role of HLA and KIR in Viral Infections. Front. Immunol. 2016, 7, 286. [CrossRef] [PubMed].
De, A.; Blotta, H.M.; Mamoni, R.L.; Louzada, P.; Bertolo, M.B.; Foss, N.T.; Moreira, A.C.; Castro, M. Effects of dexamethasone on lymphocyte proliferation and cytokine production in rheumatoid arthritis. J. Rheumatol, 2002, 29, 46-51.
Feuchtinger, T., Lang, P., Hamprecht, K., Schumm, M., Greil, J., Jahn, G., Niethammer, D. & mEinsele, H. (2004) Isolation and expansion of human adenovirus specific CD4+ and CD8+ T-cells according to IFN-gamma secretion for adjuvant immunotherapy. Experimental Hematology, 32, 282–289.
-Giles, A.J.; Hutchinson, M.-K.; Sonnemann, H.M.; Jung, J.; Fecci, P.E.; Ratnam, N.M.; Zhang,W.; Song, H.; Bailey, R.; Davis, D.;et al. Dexamethasone-induced immunosuppression: Mechanisms and implications for immunotherapy. J. Immunother. Cancer 2018, 6, 51.
Hansdottir, S.; Monick, M.M.; Hinde, S.L.; Lovan, N.; Look, D.C.; Hunninghake, G.W. Respiratory epithelial cells convert inactive vitamin D to its active form: Potential effects on host defense. J. Immunol. 2008, 181, 7090–7099.
Feuchtinger, T., Lang, P., Hamprecht, K., Schumm, M., Greil, J., Jahn, G., Niethammer, D. & Einsele, H. (2004) Isolation and expansion of human adenovirus specific CD4+ and CD8+ T-cells according to IFN-gamma secretion for adjuvant immunotherapy. Experimental Hematology, 32, 282–289.
Fu Y, Tang Z, Ye Z, Mo S, Tian X, Ni K, et al. Human adenovirus type seven infection causes a more severe disease than type 3. BMC Infect Dis. 2019 Jan 9; 19(1):32–6.
Guerrier G, Goyet S, Chheng ET, Rammaert B, Borand L, Te V, et al. Acute Viral Lower Respiratory Tract Infections in Cambodian Children Clinical and Epidemiological Characteristics. Pediatr Infect Dis J 2013; 32:e8-13.
Huang YC, Huang SL, Chen SP, Huang YL, Huang CG, Tsao KC, et al. Adenovirus infection associated with central nervous system dysfunction in children. J Clin Virol. 2013; 57(4):300–4 large retrospective review on HAdV-associated central nervous system manifestations in children in Taiwan.
Lim LM, Woo YY, De Bruyne JA, Nathan AM, Kee SY, Chan YF, et al.
Epidemiology, clinical presentation and respiratory seq-uelae of adenovirus pneumonia in children in Kuala Lumpur, Malaysia. PLoS One. 2018; 13(10):1–19.
Lion T. Adenovirus infections in immunocompetent and immunocompromised
patients. Clin Microbial Rev. 2014; 27(3):441–62 Comprehensive review on HAdV pathogenesis, diagnostics and treatment.
Lynch JP 3rd, Kajon AE. Adenovirus: epidemiology, global spread of novel
serotypes, and advances in treatment and prevention. Semin Respir Crit Care Med. 2016; 37(4):586–602 Comprehensive review on HAdV epidemiology, treatment and prevention.
Molinier-Frenkel V et al. Adenovirus hexon protein is a potent adjuvant for activation Of a cellular immune response. J Virol 2002; 76: 127–135.
Nakazawa H, Ito T, Makishima H, Misawa N, Okiyama W, Uehara T, et al.
Adenovirus fulminant hepatic failure: disseminated adenovirus disease after unrelated allogeneic stem cell transplantation for acute lymphoblastic leukemia. Intern Med 2006; 45:975-980.
National Center for Biotechnology Information (NIH)/GenBank. Human Adenovirus Working Group [Internet]. Accessed 13 April 2020. Available from: http://hadvwg.gmu.edu/
Olive M et al. The adenovirus capsid protein hexon contains a highly conserved
human CD4+ T-cell epitope. Hum Gene There 2002; 13: 1167–1178.
Ozbay Hoşnut F, Canan O, Ozçay F, Bilezikçi B. Adenovirus infection as possible
Cause of acute liver failure in a healthy child: a case report. Turk J Gastroenterol 2008; 19:281-283.
Ronchi A, Doern C, Brock E, Pugni L, Sánchez PJ. Neonatal adenoviral
Infection: a seventeen-year experience and review of the literature. J Pediatr. 2014; 164(3):529–35 largest retrospective series on HAdV infection in neonates over a 17-year period.
Russell, W.C. (2000) Update on adenovirus and its vectors. Journal of General
Virology, 81, 2573–2604.
Savon C, Acosta B, Valdes O, Goyenechea A, Gonzalez G, Pinon A, et al. A
myocarditis outbreak with fatal cases associated with adenovirus subgenera C among children from Havana City in 2005. J Clin Virol. 2008; 43(2):152–7.
Schmitz H, Wigand R, Heinrich W. Worldwide epidemiology of human adenovirus Infections. Am J Epidemiol 1983; 117:455- 466
Schwartz KL, Richardson SE, MacGregor D, Mahant S, Raghuram K, Bitnun A.
Adenovirus-associated central nervous system disease in children. J Pediatr. 2019:205, 130–7 large retrospective review on HAdV-associated central nervous system manifestations in children in Canada.
Seto D, Chodosh J, Brister JR, Jones MS. Using the wholegenome sequence to
Characterize and name human adenoviruses. J Virol. 2011; 85(11):5701–2.
Shachor-Meyouhas Y, Hadash A, Kra-Oz Z, Shafran E, Szwarcwort-Cohen M, Kassis
Adenovirus respiratory infection among immunocompetent patients in a pediatric intensive care unit during 10-year period: co-morbidity is common. Isr Med Assoc J. 2019; 21(9):595–8 large retrospective review of immunocompetent children admitted with severe HAdV infection in a pediatric intensive care unit over a 10-year period.
Siew JX, Seah XFV, Chew YR, Thoon KC, Chong CY, Yung CF, et al. Epidemiology
of adenovirus infections and outcomes of cidofovir treatment in severely Ill children. Pediatr Infect Dis J. 2020. https://doi.org/10.1097/INF.0000000000002726. Online ahead of print. PMID: 32404785 large retrospective review on cidofovir treatment in immunocompetent children.
Stephenson KE, Rhee EG, Barouch DH. Adenoviruses. In: Bennett JE, Raphael D,
Blaser MJ, editors. Mandell, Douglas, and Bennett’s principles and practice of infectious diseases. Ninth ed. Philadelphia: Elsevier; 2020. p. 1908–15.
Kaiko, G.E.; Horvat, J.C.; Beagley, K.W.; Hansbro, P.M. Immunological decision-making: How
does the immune system decide to mount a helper T-cell response? Immunology 2008, 123, 326–338.
Kenney, A.D.; Dowdle, J.A.; Bozzacco, L.; McMichael, T.M.; Gelais, C.S.; Panfil, A.R.; Sun, Y.; Schlesinger, LS.; Anderson, M.Z.;Green, PL.; et al. Human Genetic Determinants of Viral Diseases. Annu. Rev. Genet. 2017, 51, 241-263. [CrossRef];
Klemenstsson, H.; Andersson, M.; Pipkorn, U. Allergen-induced increase in nonspecific nasal
reactivity is blocked by antihistamines without a clear-cut relationship to eosinophil influx. J. Allergy Clin. Immunol. 1990, 86, 466 472. [CrossRef]
Laaksi, I.; Ruohola, J.P.; Tuohimaa, P.; Auvinen, A.; Haataja, R.; Pihlajamäki, H.; Ylikomi, T. An association of serum vitamin D concentrations <40 nmol/L with acute respiratory tract infection in young Finnish men. Am. J. Clin. Nutr. 2007, 86, 714–717.
Lee, C. Controversial Effects of Vitamin D and Related Genes on Viral Infections, Pathogenesis, and Treatment Outcomes. Nutrients 2020, 12, 962.
Medzhitov, R.; Janeway, C.A., Jr. Innate immunity: Impact on the adaptive immune response. Curr. Opin. Immunol. 1997, 9, 4–9.
Nair, R.; Kakroo, A.; Bapna, A.; Gogia, A.; Vora, A.; Pathak, A.; Korula, A.; Chakrapani, A.; Doval, D.; Prakash, G.; et al. Management of Lymphomas: Consensus Document 2018 by an Indian Expert Group. Indian J. Hematol. Blood Transfus. 2018, 34, 398-421. [CrossRef] [PubMed]
Ramamoorthy, S.; Cidlowski, J.A. Corticosteroids: Mechanisms of Action in Health and Disease. Rheum. Dis. Clin. N. Am. 2016, 42, 15–31.
Sester, M., Sester, U., Salvador, S.A., Heine, G., Lipfert, S., Girndt, M., Gartner, B. & Kohler, H. (2002) Age-related decrease in adenovirus- specific T cell responses. Journal of Infectious Diseases, 185, 1379– 1387.
Singh, R.; Kaul, R.; Kaul, A.; Khan, K. A comparative review of HLA associations with hepatitis B and C viral infections across global populations. World J. Gastroenterol. 2007, 13, 1770–1787.
Teymoori-Rad, M.; Shokri, F.; Salimi, V.; Marashi, S.M. The interplay between vitamin D and viral infections. Rev. Med. Virol. 2019, 29, e2032.
Xu,W.; Xia, S.; Pu, J.;Wang, Q.; Li, P.; Lu, L.; Jiang, S. The Antihistamine Drugs Carbinoxamine Maleate and Chlorpheniramine Maleate Exhibit Potent Antiviral Activity Against a Broad Spectrum of Influenza Viruses. Front. Microbiol. 2018, 9, 2643.
Fallaux FJ et al.New helper cells and matched early region 1-deleted adenovirus vectors human cells. In: Coligan JE et al (ed). Current Protocols in Immunology. John Wiley & Sons, Inc: New York, 1994; 1: pp 6.19.1–8.
indicator of gene expression in eukaryotic cells. Gene 1988; 66: 1–10.
Klinman DM, Nutman TB.ELISPOT Assay to detect cytokine secreting murine and
prevent generation of replication competent adenoviruses. Hum Gene Ther 1998; 9: 1909–1917.
Molinier-Frenkel V et al. Immune response to recombinant adenovirus in humans:
capsid proteins from viral input are targets for vector-specific cytotoxic T . J Virol 2000; 74 (16): 7678–7682.
Olive M et al. The adenovirus capsid protein hexon contains a highly conserved human CD4+ T-cell epitope. Hum Gene Ther 2002; 13: 1167–1178.
Copyright (c) 2024 Yasameen Waleed AL-Abedi, Ali Abdulhussein Alsaeedi, Alaa Abdalhadi Halboti
This work is licensed under a Creative Commons Attribution 4.0 International License.
