CMV and natural killer cells: shaping the response to vaccination

Abstract

Cytomegaloviruses (CMVs) are highly prevalent, persistent human pathogens that not only evade but also shape our immune responses. Natural killer (NK) cells play an important role in the control of CMV and CMVs have in turn developed a plethora of immunoevasion mechanisms targeting NK cells. This complex interplay can leave a long-lasting imprint on the immune system in general and affect responses toward other pathogens and vaccines. This review aims to provide an overview of NK cell biology and development, the manipulation of NK cells by CMVs and the potential impact of these evasion strategies on responses to vaccination.Keywords: CMV r HCMV r Immune evasion r NK cells r Vaccination IntroductionCytomegaloviruses (CMVs) are beta-herpesviruses that establish life-long persistent infection of their hosts. After resolution of acute infection, the virus enters a state of latency during which very few genes are transcribed and no new viral progeny are being generated. Latency is interrupted by occasional reactivations of the virus and expression of genes associated with the lytic virus lifecycle [1]. The success of CMVs as pathogens is a consequence of multiple immunoevasion mechanisms such as downregulation of immunoreceptor ligands or expression of decoy molecules that they employ against every arm of the immune system, including NK cells, which play an important role in the early control of virally infected and malignant cells [2]. Individuals lacking NK cells may suffer from recurrent virus infections, most commonly caused by herpes viruses and papilloma viruses, as well as increased susceptibility to malignant tumors [3][4][5]. However, in other cases, there is no obvious clinical immunodeficiency associated with the Correspondence: Dr. Vanda Juranić Lisnić e-mail: vanda.juranic@medri.uniri.hr absence of NK cells, indicating redundancy with other immune compartments for distinct genetic deficiencies [6,7]. As NK cells also regulate other arms of the immune response, their modulation by CMV can have broader consequences for immunity [8]. For instance, the strength of the primary NK cell response against the virus can have a significant impact on the adaptive immune response, although the underlying mechanisms for this are not yet clear and vary according to host and virus genotypes [9,10]. CMV infection is associated with expansion of effector memory CD8 T cell clones that are sustained for the lifetime of the host and can comprise a significant percentage of the total CD8 T cell population in aging individuals [11]. Multiple lines of evidence in experimental animals and in humans which will be discussed in this review, now indicate that CMV infection leaves a similar long-lasting imprint on NK cell phenotype and function, affecting NK cell responses to other pathogens and to vaccination.Vaccines facilitate control and eradication of infectious diseases that have plagued humanity for centuries but new infections, * Current address: Eleanor M. Riley NK cell activity depends on a balance of signals from inhibit...

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