Molecular Basis for the Recognition of Herpes Simplex Virus Type 1 Infection by Human Natural Killer Cells.

Primary infection with Herpes simplex virus type 1 (HSV1) is subclinical or only mildly symptomatic in normal individuals, yet the reason for the body's effective immune defense against this pathogen in the absence of antigen-specific immunity has not been well understood. It is clear that human natural killer (NK) cells recognize and kill HSV1-infected cells, and those individuals who either lack or have functionally impaired NK cells can suffer severe, recurrent, and sometimes fatal HSV1 infection. In this article, we review what is known about the recognition of HSV1 by NK cells, and describe a novel mechanism of innate immune surveillance against certain viral pathogens by NK cells called Fc-bridged cell-mediated cytotoxicity.

The Fc Domain of Immunoglobulin Is Sufficient to Bridge NK Cells with Virally Infected Cells.

Clearance of pathogens or tumor cells by antibodies traditionally requires both Fab and Fc domains of IgG. Here, we show the Fc domain of IgG alone mediates recognition and clearance of herpes simplex virus (HSV1)-infected cells. The human natural killer (NK) cell surface is naturally coated with IgG bound by its Fc domain to the Fcγ receptor CD16a.

Directed evolution of a virus exclusively utilizing human epidermal growth factor receptor as the entry receptor.

Rational design and directed evolution are powerful tools to generate and improve protein function; however, their uses are mostly limited to enzyme and antibody engineering. Here we describe a directed-evolution strategy, named the tandem selection and enrichment system (TSES), and its use in generating virus with exclusive specificity for a particular cellular receptor. In TSES, evolving viruses are sequentially and iteratively transferred between two different host cells, one for selection of receptor specificity and the other for enrichment of the fittest virus.

[Study on the mechanism of enhancing homing efficiency of human hematopoietic stem/progenitor cells into bone marrow after manipulation with tumor necrosis factor alpha in xenotransplanted BALB/c mouse model].

Objective: To investigate the role of tumor necrosis factor (TNF) alpha on the homing efficiency of hematopoietic stem/progenitor cells (HS/PC) into bone marrow and its mechanism.

Methods: CFSE-labeled umbilical cord blood (UCB) CD34+ cells were transplanted into irradiated (control group) or combined with TNF alpha prepared (experimental group) BALB/c recipient mice. The distribution in peripheral blood, liver, lung and homing characteristics in bone marrow and spleen of UCB CD34+ cells, in BALB/c recipient mice were determined 20 hours after xenotransplantation by flow cytometry (FACS) and their homing efficiency was calculated.