Long-term depletion of KIR3DL01+ NK cells by adeno-associated viral-vectored antibody delivery alters chronic SIV infection (doi.org)

Author summary Natural killer (NK) cells are an important early defense against viral infections, which rely on diverse surface receptors to distinguish virus-infected cells from healthy cells. Among these are the highly polymorphic killer-cell immunoglobulin-like receptors (KIRs). However, the role of individual KIR-expressing NK cell subsets during infection has been difficult to determine. We therefore utilized an adeno-associated virus (AAV) gene delivery system to selectively deplete a specific NK cell subset in rhesus macaques, an essential animal model for HIV/AIDS research. This approach resulted in long-term production of an antibody targeting the KIR3DL01 receptor, leading to rapid and sustained elimination of KIR3DL01+ NK cells in blood and tissues for more than nine months. When these animals were infected with simian immunodeficiency virus (SIV), a close relative of HIV, KIR3DL01-depleted animals showed a modest increase in viral loads during chronic infection compared to