The reference OMIM entry for this protein is 604522

Defensin, alpha, 3; defa3
Def3
Human neutrophil peptide 3; hnp3

DESCRIPTION

See DEFA1 (125220) for background information on defensins. DEFA1 and DEFA3 differ from each other only by their N-terminal amino acids (ala and asp, respectively). DEFA2 is identical to both except that it lacks this N-terminal amino acid.

GENE FUNCTION

Walker et al. (1986) described an anti-human immunodeficiency virus (HIV) factor secreted by CD8 (see 186910) T cells from certain HIV-1-infected individuals in a non-major histocompatibility complex (MHC) class I-restricted and non-cell contact-dependent manner. The factor, referred to as CAF (CD8 antiviral factor), is resistant to heat and acid and is of low molecular mass. CAF is produced at relatively higher levels by clinically stable HIV-1-infected patients, the so-called long-term nonprogressors (LTNPs), but not by progressors. Cocchi et al. (1995) determined that the beta chemokines CCL5 (187011), CCL4 (182284), and CCL3 (182283) possess CAF-like activity, but only against macrophage-tropic and not T-cell-tropic viral isolates, because of their common usage of CCR5 (601373). Using a protein chip system and mass spectrometric and protein database analyses, Zhang et al. (2002) identified a cluster of three 3.3- to 3.5-kD proteins, DEFA1, DEFA2, and DEFA3, secreted by LTNPs and most normal individuals, but not by progressors. DEFA1-, DEFA2-, and DEFA3-specific antibodies depleted antiviral activity in a dose-dependent manner, particularly against viruses using CXCR4 (162643) rather than CCR5 as a coreceptor. Addition of synthetic or purified natural defensins inhibited HIV-1 replication in vitro. Flow cytometric analysis determined that in addition to neutrophils, a small population of CD8-positive T lymphocytes harbor and secrete DEFA1, DEFA2, and DEFA3. Zhang et al. (2002) proposed that these defensins account for much of the anti-HIV-1 activity of CAF that is not attributable to beta chemokines. Chang et al. (2003) investigated whether DEFAs, particularly DEFA1, contribute to CAF-mediated inhibition of HIV-1 transcription. They found that DEFA1 inhibited HIV-1 infection following viral entry, but that the DEFAs were not involved in the inhibition of HIV-1 gene expression and long terminal repeat activation attributed to CAF derived from herpesvirus saimiri-transformed CD8-positive cells. Independently, Mackewicz et al. (2003) showed that DEFA1, DEFA2, and DEFA3 exhibit anti-HIV activity by directly inactivating HIV particles and by reducing the ability of CD4-positive T lymphocytes to replicate the virus. Immunocytochemical and RT-PCR analysis detected expression of DEFAs in neutrophils and monocytes, but not in CD8-positive T cells. Antibodies specific for the DEFAs did not block the antiviral activity of CAF-active CD8-positive cell culture fluids, indicating that, although DEFAs possess anti-HIV effects, they are distinct from CAF. In a retraction based upon RT-PCR analysis and careful dissection of their cell culture system, Zhang et al. (2002) concluded that their initial interpretation of a possible CD8-positive T-lymphocyte source for DEFAs was incorrect. CAF activity from CD8-positive cells, in the absence of contaminating neutrophil feeder cells, could not be attributed to DEFAs. However, neutrophil-derived DEFAs did have potent anti-HIV-1 activity, regardless of viral strain or target cell. Anthrax lethal toxin, a combination of the bacterium's lethal factor and protective antigen proteins, plays a major role in anthrax pathogenesis. K ... More on the omim web site

Subscribe to this protein entry history

Oct. 20, 2018: Protein entry updated
Automatic update: OMIM entry 604522 was added.

Oct. 19, 2018: Additional information
Initial protein addition to the database. This entry was referenced in Bryk and co-workers. (2017).