Latent herpesvirus infection arms NK cells

Division of Rheumatology, Department of Internal Medicine, Washington University School of Medicine, St Louis, MO 63110, USA.
Blood (Impact Factor: 10.43). 02/2010; 115(22):4377-83. DOI: 10.1182/blood-2009-09-245464
Source: PubMed

ABSTRACT Natural killer (NK) cells were identified by their ability to kill target cells without previous sensitization. However, without an antecedent "arming" event, NK cells can recognize, but are not equipped to kill, target cells. How NK cells become armed in vivo in healthy hosts is unclear. Because latent herpesviruses are highly prevalent and alter multiple aspects of host immunity, we hypothesized that latent herpesvirus infection would arm NK cells. Here we show that NK cells from mice latently infected with Murid herpesvirus 4 (MuHV-4) were armed as evidenced by increased granzyme B protein expression, cytotoxicity, and interferon-gamma production. NK-cell arming occurred rapidly in the latently infected host and did not require acute viral infection. Furthermore, NK cells armed by latent infection protected the host against a lethal lymphoma challenge. Thus, the immune environment created by latent herpesvirus infection provides a mechanism whereby host NK-cell function is enhanced in vivo.

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    • "Either this immunomodulation or latency-associated innate immune activation, as shown for MuHV-4 in laboratory mice (Barton et al., 2007), could underlie the survival cost observed here. For example, although a state of heightened immune activation has been shown to protect against bacterial challenge and lethal lymphoma in laboratory mice (Barton et al., 2007; White et al., 2010), it could be costly in the wild. Immune activation may reduce resources available for other important physiological functions or cause immunopathology (Eraud et al., 2005; Bertrand et al., 2006; Hanssen, 2006). "
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