TY - JOUR
T1 - Human NK Cells and Herpesviruses
T2 - Mechanisms of Recognition, Response and Adaptation
AU - Della Chiesa, Mariella
AU - De Maria, Andrea
AU - Muccio, Letizia
AU - Bozzano, Federica
AU - Sivori, Simona
AU - Moretta, Lorenzo
PY - 2019/10/4
Y1 - 2019/10/4
N2 - NK cells contribute to early defenses against viruses through their inborn abilities that include sensing of PAMPs and inflammatory signals such as cytokines or chemokines, recognition, and killing of infected cells through activating surface receptors engagement. Moreover, they support adaptive responses via Ab-dependent mechanisms, triggered by CD16, and DC editing. Their fundamental role in anti-viral responses has been unveiled in patients with NK cell deficiencies suffering from severe Herpesvirus infections. Notably, these infections, often occurring as primary infections early in life, can be efficiently cleared by NK, T, and B cells in healthy hosts. Herpesviruses however, generate a complicated balance with the host immune system through their latency cycle moving between immune control and viral reactivation. This lifelong challenge has contributed to the development of numerous evasion mechanisms by Herpesviruses, many of which devoted to elude NK cell surveillance from viral reactivations rather than primary infections. This delicate equilibrium can be altered in proportions of healthy individuals promoting virus reactivation and, more often, in immunocompromised subjects. However, the constant stimulus provided by virus-host interplay has also favored NK-cell adaptation to Herpesviruses. During anti-HCMV responses, NK cells can reshape their receptor repertoire and function, through epigenetic remodeling, and acquire adaptive traits such as longevity and clonal expansion abilities. The major mechanisms of recognition and effector responses employed by NK cells against Herpesviruses, related to their genomic organization will be addressed, including those allowing NK cells to generate memory-like responses. In addition, the mechanisms underlying virus reactivation or control will be discussed.
AB - NK cells contribute to early defenses against viruses through their inborn abilities that include sensing of PAMPs and inflammatory signals such as cytokines or chemokines, recognition, and killing of infected cells through activating surface receptors engagement. Moreover, they support adaptive responses via Ab-dependent mechanisms, triggered by CD16, and DC editing. Their fundamental role in anti-viral responses has been unveiled in patients with NK cell deficiencies suffering from severe Herpesvirus infections. Notably, these infections, often occurring as primary infections early in life, can be efficiently cleared by NK, T, and B cells in healthy hosts. Herpesviruses however, generate a complicated balance with the host immune system through their latency cycle moving between immune control and viral reactivation. This lifelong challenge has contributed to the development of numerous evasion mechanisms by Herpesviruses, many of which devoted to elude NK cell surveillance from viral reactivations rather than primary infections. This delicate equilibrium can be altered in proportions of healthy individuals promoting virus reactivation and, more often, in immunocompromised subjects. However, the constant stimulus provided by virus-host interplay has also favored NK-cell adaptation to Herpesviruses. During anti-HCMV responses, NK cells can reshape their receptor repertoire and function, through epigenetic remodeling, and acquire adaptive traits such as longevity and clonal expansion abilities. The major mechanisms of recognition and effector responses employed by NK cells against Herpesviruses, related to their genomic organization will be addressed, including those allowing NK cells to generate memory-like responses. In addition, the mechanisms underlying virus reactivation or control will be discussed.
KW - activating receptors
KW - Herpesvirus
KW - memory responses
KW - NK cells
KW - TLRs
KW - viral reactivation
UR - http://www.scopus.com/inward/record.url?scp=85073686398&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85073686398&partnerID=8YFLogxK
U2 - 10.3389/fmicb.2019.02297
DO - 10.3389/fmicb.2019.02297
M3 - Review article
AN - SCOPUS:85073686398
VL - 10
JO - Frontiers in Microbiology
JF - Frontiers in Microbiology
SN - 1664-302X
M1 - 2297
ER -