Abstract
The compound genotype KIR3DS1/HLA-B Bw4-80I, which presumably favors natural killer cell activation, has been implicated in protection against HIV disease. We show that this genotype confers dual protection over the course of HIV disease; early direct containment of HIV viral load, and late specific defense against opportunistic infections, but not AIDS-related malignancies. The double protection of KIR3DS1/Bw4-80I in an etiologically complex disease such as AIDS, along with the disease specificity of its effects is conceptually novel and underscores the intricacy of host immunogenetics against HIV/AIDS.
Highlights
Natural killer (NK) cells are central components of the innate immune response, providing early defense against viral infections and tumor cells by production of cytokines and direct cytotoxicity [1,2]
The group of killer immunoglobulin-like receptors (KIR) on NK cells, which contains allotypes that are either activating or inhibitory, participate in the complex regulation of NK cell responses through recognition of specific human leukocyte antigen (HLA) class I molecules on target cells [3]
KIR and HLA loci are both highly polymorphic and they map to distinct human chromosomes (Chromosomes 19 and 6, respectively), and they segregate independently. Both the KIR receptor and its specific HLA ligand must be present in order to regulate NK cell activity, such that one without the other is functionally inert
Summary
The compound genotype KIR3DS1/HLA-B Bw4-80I, which presumably favors natural killer cell activation, has been implicated in protection against HIV disease. We show that this genotype confers dual protection over the course of HIV disease; early direct containment of HIV viral load, and late specific defense against opportunistic infections, but not AIDS-related malignancies. The double protection of KIR3DS1/Bw4-80I in an etiologically complex disease such as AIDS, along with the disease specificity of its effects is conceptually novel and underscores the intricacy of host immunogenetics against HIV/AIDS
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