NK Cell Receptor Protects Mice Specifically Against Cytomegalovirus (CMV)

Human cytomegalovirus (HCMV) is the leading cause of congenital (present at birth) viral disease and opportunistic infection of immunocompromised patients. This is due to the high prevalence of the virus, with up to 90% and 50% of the urban and rural populations infected, respectively. The virus's slow growth cycle allows co-survival of both infected cell and virus, so infection is generally asymptomatic. The virus, however, is never eliminated; rather, it remains latent in tissues of the host, and is reactivated in immunocompromised individuals such as people with HIV or allograft recipients. These people have impairments in both cell-mediated and antibody-mediated immunities. In rare instances, however, severe illness occurs in fetuses and newborns without known immunological impairment. It is thought that a type of blood cell, called the Natural Killer (NK) cell, controls viral infection, but definitive proof has been lacking. In this issue (Nature Genetics, Vol. 28, No. 1, 01 May 2001), Silvia Vidal (of University of Toronto, Canada) and colleagues provide support for this hypothesis: they identify a NK cell receptor that protects mice specifically against cytomegalovirus (CMV).

It was previously established that infection by CMV in the mouse is controlled by a gene or genes that lie in a region of chromosome 4 that contains a cluster of genes encoding NK cell receptors. In the current study, Vidal and colleagues show that a gene called Klra8 (also known as Ly49H) that encodes a stimulatory receptor expressed on the surface of NK cells allows the detection and destruction of CMV-infected cells. As Jean-Laurent Casanova and colleagues (of Necker Medical School, Paris, France) discuss in an accompanying News & Views article, Klra8 could have evolved to protect against CMV.

In contrast with T and B lymphocytes, NK cells produce a relatively modest repertoire of surface receptors and are not selected in response to specific infectious agents. The study provides the first genetic evidence for a specific role of NK cells in pathogen-specific immune response and provides some helpful pointers for studies of human immunity to HCMV.

CONTACT:

Dr. Silvia Vidal
University of Ottawa
Ottawa, Ontario - Canada
Telephone: +1 613-562-5800 x 8073
Fax: +1 613-526-5452
Email: svidal@uottawa.ca

Dr. Jean-Laurent Casanova
Hopital Necker-Enfants Malades
Paris - France
Telephone: +33 1-40-61-56-87
Fax: +33 1-40-61-56-88
Email: casanova@necker.fr

(C) Nature Genetics press release.

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