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Role of antibodies in confining cytomegalovirus after reactivation from latency: three decades’ résumé

Abstract

Cytomegaloviruses (CMVs) are highly prevalent herpesviruses, characterized by strict species specificity and the ability to establish non-productive latent infection from which reactivation can occur. Reactivation of latent human CMV (HCMV) represents one of the most important clinical challenges in transplant recipients secondary to the strong immunosuppression. In addition, HCMV is the major viral cause of congenital infection with severe sequelae including brain damage. The accumulated evidence clearly shows that cellular immunity plays a major role in the control of primary CMV infection as well as establishment and maintenance of latency. However, the efficiency of antiviral antibodies in virus control, particularly in prevention of congenital infection and virus reactivation from latency in immunosuppressed hosts, is much less understood. Because of a strict species specificity of HCMV, the role of antibodies in controlling CMV disease has been addressed using murine CMV (MCMV) as a model. Here, we review and discuss the role played by the antiviral antibody response during CMV infections with emphasis on latency and reactivation not only in the MCMV model, but also in relevant clinical settings. We provide evidence to conclude that antiviral antibodies do not prevent the initiating molecular event of virus reactivation from latency but operate by preventing intra-organ spread and inter-organ dissemination of recurrent virus.

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Fig. 1

Adapted from ©1994 JONJIĆ et al. Originally published in Journal of Experimental Medicine. https://doi.org/10.1084/JEM.179.5.1713 [27]

Fig. 2

Adapted from ©1998 POLIĆ et al. Originally published in Journal of Experimental Medicine. https://doi.org/10.1084/jem.188.6.1047 [41]

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Acknowledgements

S.J. has been supported by the grant “Strengthening the capacity of CerVirVac for research in virus immunology and vaccinology”, KK.01.1.1.01.0006, awarded to the Scientific Centre of Excellence for Virus Immunology and Vaccines and co-financed by the European Regional Development Fund. W.J.B. has been supported by NIH R01 DC015980-01A1 and AI089956. A.K. has been supported by Croatian Science Foundation under the project IP-2018-01-9086. M.J.R. receives funding from the Deutsche Forschungsgemeinschaft, SFB1292, individual project TP11.

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Correspondence to Stipan Jonjić.

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This article is part of the Special Issue on Immunological Imprinting during Chronic Viral Infection.

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Krmpotić, A., Podlech, J., Reddehase, M.J. et al. Role of antibodies in confining cytomegalovirus after reactivation from latency: three decades’ résumé. Med Microbiol Immunol 208, 415–429 (2019). https://doi.org/10.1007/s00430-019-00600-1

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Keywords

  • Antibodies
  • Cytomegalovirus
  • Immunotherapy
  • Latency
  • Passive immunization
  • Reactivation
  • Recurrence
  • Serum transfer
  • Viral entry complexes
  • Virus dissemination
  • Virus spread