The infectivity of progeny adenovirus in the presence of neutralizing antibody Open Access

Abstract

Human adenoviruses (Ads), common pathogens that cause upper respiratory and gastrointestinal infections, are blocked by neutralizing antibodies (nAbs). However, Ads are not fully eliminated even in hosts with nAbs. In this study, we assessed the infectivity of progeny Ad serotype 5 (Ad5) in the presence of nAb. The infectivity of Ad5 was evaluated according to the expression of the Ad genome and reporter gene. Infection by wild-type Ad5 and Ad5 vector continued to increase until 3 days after infection even in the presence of nAb. We established an assay for determining the infection levels of progeny Ad5 using a sorting system with magnetic beads and observed little difference in progeny Ad5 counts in the presence and absence of nAb 1 day after infection. Moreover, progeny Ad5 in the presence of nAb more effectively infected coxsackievirus and adenovirus receptor (CAR)-positive cells than CAR-negative cells. We investigated the function of fiber proteins, which are the binding partners of CAR, during secondary infection, observing that fibre proteins spread from infected cells to adjacent cells in a CAR-dependent manner. In conclusion, this study revealed that progeny Ad5 could infect cells even in the presence of nAb, differing from the common features of the Ad5 infection cycle. Our findings may be useful for developing new therapeutic agents against Ad infection.

Funding
This study was supported by the:
  • Scholarship Fund for Young Researchers of The Promotion and Mutual Aid Corporation for Private Schools of Japan.
    • Principle Award Recipient: TakamasaHirai
  • a Grant-in-Aid for Young Scientists of Showa Pharmaceutical University
    • Principle Award Recipient: TakamasaHirai
Loading

Article metrics loading...

/content/journal/jgv/10.1099/jgv.0.001590
2021-04-12
2024-03-29
Loading full text...

Full text loading...

/deliver/fulltext/jgv/102/4/jgv001590.html?itemId=/content/journal/jgv/10.1099/jgv.0.001590&mimeType=html&fmt=ahah

References

  1. Baldwin A, Kingman H, Darville M, Foot AB, Grier D et al. Outcome and clinical course of 100 patients with adenovirus infection following bone marrow transplantation. Bone Marrow Transplant 2000; 26:1333–1338 [View Article][PubMed]
    [Google Scholar]
  2. Pham TTN, Burchette JL, Hale LP. Fatal disseminated adenovirus infections in immunocompromised patients. Am J Clin Pathol 2003; 120:575–583 [View Article][PubMed]
    [Google Scholar]
  3. Cederwall S, Påhlman LI. Respiratory adenovirus infections in immunocompetent and immunocompromised adult patients. Epidemiol Infect 2020; 147:e328 [View Article][PubMed]
    [Google Scholar]
  4. Henry LJ, Xia D, Wilke ME, Deisenhofer J, Gerard RD. Characterization of the knob domain of the adenovirus type 5 fiber protein expressed in Escherichia coli. J Virol 1994; 68:5239–5246 [View Article][PubMed]
    [Google Scholar]
  5. Roelvink PW, Lizonova A, Lee JG, Li Y, Bergelson JM et al. The coxsackievirus-adenovirus receptor protein can function as a cellular attachment protein for adenovirus serotypes from subgroups A, C, D, E, and F. J Virol 1998; 72:7909–7915 [View Article][PubMed]
    [Google Scholar]
  6. Wickham TJ, Filardo EJ, Cheresh DA, Nemerow GR. Integrin alpha v beta 5 selectively promotes adenovirus mediated cell membrane permeabilization. J Cell Biol 1994; 127:257–264 [View Article][PubMed]
    [Google Scholar]
  7. Chiu CY, Mathias P, Nemerow GR, Stewart PL. Structure of adenovirus complexed with its internalization receptor, alphavbeta5 integrin. J Virol 1999; 73:6759–6768 [View Article][PubMed]
    [Google Scholar]
  8. Suomalainen M, Nakano MY, Keller S, Boucke K, Stidwill RP et al. Microtubule-dependent plus- and minus end-directed motilities are competing processes for nuclear targeting of adenovirus. J Cell Biol 1999; 144:657–672 [View Article]
    [Google Scholar]
  9. Leopold PL, Kreitzer G, Miyazawa N, Rempel S, Pfister KK et al. Dynein- and microtubule-mediated translocation of adenovirus serotype 5 occurs after endosomal lysis. Hum Gene Ther 2000; 11:151–165 [View Article][PubMed]
    [Google Scholar]
  10. Spindler KR, Eng CY, Berk AJ. An adenovirus early region 1A protein is required for maximal viral DNA replication in growth-arrested human cells. J Virol 1985; 53:742–750 [View Article][PubMed]
    [Google Scholar]
  11. Hu MC, Hsu MT. Adenovirus E1B 19K protein is required for efficient DNA replication in U937 cells. Virology 1997; 227:295–304 [View Article][PubMed]
    [Google Scholar]
  12. Tollefson AE, Scaria A, Hermiston TW, Ryerse JS, Wold LJ et al. The adenovirus death protein (E3-11.6K) is required at very late stages of infection for efficient cell lysis and release of adenovirus from infected cells. J Virol 1996; 70:2296–2306 [View Article][PubMed]
    [Google Scholar]
  13. Yakimovich A, Gumpert H, Burckhardt CJ, Lütschg VA, Jurgeit A et al. Cell-Free transmission of human adenovirus by passive mass transfer in cell culture simulated in a computer model. J Virol 2012; 86:10123–10137 [View Article][PubMed]
    [Google Scholar]
  14. Basner-Tschakarjan E, Gaffal E, O'Keeffe M, Tormo D, Limmer A et al. Adenovirus efficiently transduces plasmacytoid dendritic cells resulting in TLR9-dependent maturation and IFN-alpha production. J Gene Med 2006; 8:1300–1306 [View Article][PubMed]
    [Google Scholar]
  15. Yamaguchi T, Kawabata K, Kouyama E, Ishii KJ, Katayama K et al. Induction of type I interferon by adenovirus-encoded small RNAs. Proc Natl Acad Sci U S A 2010; 107:17286–17291 [View Article][PubMed]
    [Google Scholar]
  16. Ackrill AM, Foster GR, Laxton CD, Flavell DM, Stark GR et al. Inhibition of the cellular response to interferons by products of the adenovirus type 5 E1A oncogene. Nucleic Acids Res 1991; 19:4387–4393 [View Article][PubMed]
    [Google Scholar]
  17. Olanubi O, Frost JR, Radko S, Pelka P. Suppression of type I interferon signaling by E1A via RuvBL1/Pontin. J Virol 2017; 91:pii: e02484–16 [View Article][PubMed]
    [Google Scholar]
  18. Bridge E, Ketner G. Redundant control of adenovirus late gene expression by early region 4. J Virol 1989; 63:631–638 [View Article][PubMed]
    [Google Scholar]
  19. Huang MM, Hearing P. Adenovirus early region 4 encodes two gene products with redundant effects in lytic infection. J Virol 1989; 63:2605–2615 [View Article][PubMed]
    [Google Scholar]
  20. Ullman AJ, Reich NC, Hearing P. Adenovirus E4 ORF3 protein inhibits the interferon-mediated antiviral response. J Virol 2007; 81:4744–4752 [View Article][PubMed]
    [Google Scholar]
  21. Tang J, Olive M, Pulmanausahakul R, Schnell M, Flomenberg N et al. Human CD8+ cytotoxic T cell responses to adenovirus capsid proteins. Virology 2006; 350:312–322 [View Article][PubMed]
    [Google Scholar]
  22. Leen AM, Christin A, Khalil M, Weiss H, Gee AP et al. Identification of hexon-specific CD4 and CD8 T-cell epitopes for vaccine and immunotherapy. J Virol 2008; 82:546–554 [View Article][PubMed]
    [Google Scholar]
  23. Roberts DM, Nanda A, Havenga MJE, Abbink P, Lynch DM et al. Hexon-chimaeric adenovirus serotype 5 vectors circumvent pre-existing anti-vector immunity. Nature 2006; 441:239–243 [View Article][PubMed]
    [Google Scholar]
  24. Bradley RR, Lynch DM, Iampietro MJ, Borducchi EN, Barouch DH. Adenovirus serotype 5 neutralizing antibodies target both hexon and fiber following vaccination and natural infection. J Virol 2012; 86:625–629 [View Article][PubMed]
    [Google Scholar]
  25. Seshidhar Reddy P, Ganesh S, Limbach MP, Brann T, Pinkstaff A et al. Development of adenovirus serotype 35 as a gene transfer vector. Virology 2003; 311:384–393 [View Article][PubMed]
    [Google Scholar]
  26. Veltrop-Duits LA, van Vreeswijk T, Heemskerk B, Thijssen JCP, El Seady R et al. High titers of pre-existing adenovirus serotype-specific neutralizing antibodies in the host predict viral reactivation after allogeneic stem cell transplantation in children. Clin Infect Dis 2011; 52:1405–1413 [View Article][PubMed]
    [Google Scholar]
  27. Dull T, Zufferey R, Kelly M, Mandel RJ, Nguyen M et al. A third-generation lentivirus vector with a conditional packaging system. J Virol 1998; 72:8463–8471 [View Article][PubMed]
    [Google Scholar]
  28. Yee JK, Friedmann T, Burns JC. Generation of high-titer pseudotyped retroviral vectors with very broad host range. Methods Cell Biol 1994; 43 Pt A:99–112 [View Article][PubMed]
    [Google Scholar]
  29. Koizumi N, Mizuguchi H, Sakurai F, Yamaguchi T, Watanabe Y et al. Reduction of natural adenovirus tropism to mouse liver by fiber-shaft exchange in combination with both CAR- and alphav integrin-binding ablation. J Virol 2003; 77:13062–13072 [View Article][PubMed]
    [Google Scholar]
  30. Maizel JV, White DO, Scharff MD. The polypeptides of adenovirus. I. Evidence for multiple protein components in the virion and a comparison of types 2, 7a, and 12. Virology 1968; 36:115–125 [View Article][PubMed]
    [Google Scholar]
  31. Sato A, Hirai T, Koizumi N, Hatakeyama S, Watanabe A et al. Adenovirus fiber can distribute itself to the cell surface without membrane damage. BPB Reports 2019; 2:113–118 [View Article]
    [Google Scholar]
  32. Garnett CT, Erdman D, Xu W, Gooding LR. Prevalence and quantitation of species C adenovirus DNA in human mucosal lymphocytes. J Virol 2002; 76:10608–10616 [View Article]
    [Google Scholar]
  33. Lichtenstein DL, Wold WSM. Experimental infections of humans with wild-type adenoviruses and with replication-competent adenovirus vectors: replication, safety, and transmission. Cancer Gene Ther 2004; 11:819–829 [View Article][PubMed]
    [Google Scholar]
  34. Alkhalaf MA, Guiver M, Cooper RJ. Prevalence and quantitation of adenovirus DNA from human tonsil and adenoid tissues. J Med Virol 2013; 85:1947–1954 [View Article][PubMed]
    [Google Scholar]
  35. Burckhardt CJ, Suomalainen M, Schoenenberger P, Boucke K, Hemmi S et al. Drifting motions of the adenovirus receptor CAR and immobile integrins initiate virus uncoating and membrane lytic protein exposure. Cell Host Microbe 2011; 10:105–117 [View Article][PubMed]
    [Google Scholar]
  36. Sakai T, Nishimura SI, Naito T, Saito M. Influenza A virus hemagglutinin and neuraminidase act as novel motile machinery. Sci Rep 2017; 7:45043 [View Article][PubMed]
    [Google Scholar]
  37. Bewley MC, Springer K, Zhang YB, Freimuth P, Flanagan JM. Structural analysis of the mechanism of adenovirus binding to its human cellular receptor, CAR. Science 1999; 286:1579–1583 [View Article][PubMed]
    [Google Scholar]
  38. Cohen CJ, Shieh JT, Pickles RJ, Okegawa T, Hsieh JT et al. The coxsackievirus and adenovirus receptor is a transmembrane component of the tight junction. Proc Natl Acad Sci U S A 2001; 98:15191–15196 [View Article][PubMed]
    [Google Scholar]
  39. Patzke C, Max KEA, Behlke J, Schreiber J, Schmidt H et al. The coxsackievirus-adenovirus receptor reveals complex homophilic and heterophilic interactions on neural cells. J Neurosci 2010; 30:2897–2910 [View Article][PubMed]
    [Google Scholar]
  40. Gupta P, Balachandran R, Ho M, Enrico A, Rinaldo C. Cell-to-cell transmission of human immunodeficiency virus type 1 in the presence of azidothymidine and neutralizing antibody. J Virol 1989; 63:2361–2365 [View Article][PubMed]
    [Google Scholar]
  41. Liles WC, Cushing H, Holt S, Bryan C, Hackman RC. Severe adenoviral nephritis following bone marrow transplantation: successful treatment with intravenous ribavirin. Bone Marrow Transplant 1993; 12:409–412[PubMed]
    [Google Scholar]
  42. Miyamura K, Hamaguchi M, Taji H, Kanie T, Kohno A et al. Successful ribavirin therapy for severe adenovirus hemorrhagic cystitis after allogeneic marrow transplant from close HLA donors rather than distant donors. Bone Marrow Transplant 2000; 25:545–548 [View Article][PubMed]
    [Google Scholar]
  43. Legrand F, Berrebi D, Houhou N, Freymuth F, Faye A et al. Early diagnosis of adenovirus infection and treatment with cidofovir after bone marrow transplantation in children. Bone Marrow Transplant 2001; 27:621–626 [View Article][PubMed]
    [Google Scholar]
  44. Yusuf U, Hale GA, Carr J, Gu Z, Benaim E et al. Cidofovir for the treatment of adenoviral infection in pediatric hematopoietic stem cell transplant patients. Transplantation 2006; 81:1398–1404 [View Article][PubMed]
    [Google Scholar]
  45. Feucht J, Opherk K, Lang P, Kayser S, Hartl L et al. Adoptive T-cell therapy with hexon-specific Th1 cells as a treatment of refractory adenovirus infection after HSCT. Blood 2015; 125:1986–1994 [View Article][PubMed]
    [Google Scholar]
  46. Feuchtinger T, Matthes-Martin S, Richard C, Lion T, Fuhrer M et al. Safe adoptive transfer of virus-specific T-cell immunity for the treatment of systemic adenovirus infection after allogeneic stem cell transplantation. Br J Haematol 2006; 134:64–76 [View Article][PubMed]
    [Google Scholar]
  47. Permpalung N, Mahoney MV, Alonso CD. Adjunctive use of cidofovir and intravenous immunoglobulin to treat invasive adenoviral disease in solid organ transplant recipients. Pharmacotherapy 2018; 38:1260–1266 [View Article][PubMed]
    [Google Scholar]
  48. Serrano RM, Darragh RK, Parent JJ. Successful treatment of disseminated adenovirus infection with cidofovir and intravenous immunoglobulin in an infant following heart transplant. Cardiol Young 2018; 28:888–889 [View Article][PubMed]
    [Google Scholar]
  49. Park UJ, Hyun SK, Kim HT, Cho WH, Han SY. Successful treatment of disseminated adenovirus infection with ribavirin and intravenous immunoglobulin in an adult renal transplant recipient: a case report. Transplant Proc 2015; 47:791–793 [View Article][PubMed]
    [Google Scholar]
  50. Piedra PA, Kasel JA, Norton HJ, Gruber WC, Garcia-Prats JA et al. Evaluation of an intravenous immunoglobulin preparation for the prevention of viral infection among hospitalized low birth weight infants. Pediatr Infect Dis J 1990; 9:470–475 [View Article][PubMed]
    [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/jgv/10.1099/jgv.0.001590
Loading
/content/journal/jgv/10.1099/jgv.0.001590
Loading

Data & Media loading...

Supplements

Supplementary material 1

PDF

Most cited Most Cited RSS feed