Viruses gain entry into cells by means of receptors encoded by genes of the host cell. Herpes simplex virus (HSV) has
been shown to infect cells, including activated T lymphocytes, by means of an HSV envelope glycoprotein D attaching
to the herpesvirus entry mediator (HVEM), a member of the tumor necrosis factor receptor superfamily (TNFRSF14).
Mauri et al. (1998) demonstrated that HVEM binds 2 cellular ligands, secreted lymphotoxin A (LTA) and
LIGHT (for homologous to lymphotoxins, exhibits inducible expression, and competes with HSV glycoprotein D for
HVEM, a receptor expressed by T lymphocytes). By screening activated T cells by FACS for staining with a surrogate
receptor composed of the extracellular domain of HVEM and the Fc of IgG, they determined by
competition experiments that HVEM binds with LTA and a 29- to 30-kD protein but not with lymphotoxin B (LTB;
) or tumor necrosis factor-alpha (TNFA). By screening an activated T-cell library, they identified a
TNFSF-like cDNA (LIGHT, or TNFSF14), which encodes a 240-amino acid protein with a 37-amino acid N-terminal
cytosolic domain and a 22-amino acid type II transmembrane stretch. In the C-terminal receptor-binding domain, LIGHT
exhibits 34% identity with LTB and 31% identity with FASL (TNSF6; 134638) and lesser identity with other TNFSFs.
NCBI Summary:
The protein encoded by this gene is a member of the tumor necrosis factor (TNF) ligand family. This protein is a ligand for TNFRSF14, which is a member of the tumor necrosis factor receptor superfamily, and which is also known as a herpesvirus entry mediator (HVEM). This protein may function as a costimulatory factor for the activation of lymphoid cells and as a deterrent to infection by herpesvirus. This protein has been shown to stimulate the proliferation of T cells, and trigger apoptosis of various tumor cells. This protein is also reported to prevent tumor necrosis factor alpha mediated apoptosis in primary hepatocyte. Two alternatively spliced transcript variant encoding distinct isoforms have been reported.
Morrison LJ, et al 2002 reported that tumor necrosis factor alpha enhances oocyte/follicle apoptosis
in the neonatal rat ovary.
The presence of both
TNFalpha and its receptors in the neonatal rat ovary suggests a potential role
for it in follicle assembly or oocyte atresia. Previous studies have provided
support for effects of TNFalpha on isolated granulosa and theca cells and
intact follicles; however, this is the first study to
investigate the effects of TNFalpha on the earliest stages of follicular
development. Effects of TNFalpha on oocyte/follicle number and apoptosis were
investigated using an ovarian organ-culture system that supported assembly of
primordial follicles in vitro. Ovaries were collected on the day of birth and
treated with TNFalpha (0, 0.1, 1.0, 10, or 50 ng/ml), a function-blocking
TNFalpha antibody (5 mug/ml), or control immunoglobulin (Ig) G. At I ng/ml,
TNFalpha decreased follicle and oocyte numbers during 3 days of cultured
whereas higher (10 and 50 ng/ml) or lower (0.1 ng/ml) doses had no effect.
Treatment with TNFalpha antibodies increased the number of oocytes and
follicles compared to nonspecific IgG control. At I ng/ml, TNFalpha increased
apoptotic DNA laddering twofold, with no significant effect from lower or
higher doses. The cells undergoing apoptosis, as determined by in situ
end-labeling, were oocytes, interstitial cells, and granulosa. cells. These
findings suggest that TNFalpha may be involved in oocyte atresia that normally
occurs during the perinatal period.
Expression regulated by
Comment
Ovarian localization
Oocyte
Comment
Neilson L, et al 200 reported molecular phenotyping of the human oocyte by PCR-SAGE.
Consecutive application of PCR and serial analysis of gene expression (SAGE) was used to generate a
catalog of approximately 50,000 SAGEtags from nine human oocytes. Matches for known genes were
identified using the National Institutes of Health SAGEtag database. Matches in the oocyte SAGE catalog
were found for surface receptors, second-messenger systems, and cytoskeletal, apoptotic, and secreted
proteins, including LIGHT.