NK cells play a critical role in early viral control by either killing infected cells or releasing antimicrobial cytokines. They recognize infected cells through a balance of inhibitory and activating receptors. Viruses have evolved various strategies to modulate NK cell activity, including downregulating MHC I molecules, interfering with NK cell receptors, and using viral miRNAs. These mechanisms help viruses evade NK cell recognition and enhance their pathogenicity. Viruses such as influenza, hepatitis C, and cytomegalovirus (CMV) directly target NK cells or their receptors. For example, influenza virus can infect NK cells and induce apoptosis, while CMV encodes proteins that downregulate MHC I molecules and use MHC surrogates to avoid detection. HCMV also employs miRNAs to suppress MHC I expression, which helps it evade NK cell recognition. CMV is particularly adept at manipulating NK cell receptors, using MHC I surrogates like HLA-E and Qa-1 to mimic MHC I molecules and avoid detection. It also modulates NKG2D and Ly49 receptors, which are crucial for NK cell activation. Other viruses, such as flaviviruses, upregulate MHC I to avoid NK cell recognition, even though this makes them more susceptible to CD8+ T cell responses. Viruses also interfere with NK cell activation by blocking receptors or their ligands. For instance, HCMV targets NKG2D ligands and uses miRNAs to suppress their expression. Similarly, Kaposi's sarcoma-associated herpesvirus (KSHV) downregulates NKG2D ligands and NKp80 ligands to avoid NK cell-mediated lysis. NK cells can also acquire memory-like functions, which may enhance their ability to respond to viral infections. However, viruses have evolved strategies to counteract this, such as generating escape mutants that evade NK cell recognition. The interplay between NK cells and viruses highlights the ongoing evolutionary arms race, with viruses constantly adapting to evade immune detection while hosts develop mechanisms to combat viral infections.NK cells play a critical role in early viral control by either killing infected cells or releasing antimicrobial cytokines. They recognize infected cells through a balance of inhibitory and activating receptors. Viruses have evolved various strategies to modulate NK cell activity, including downregulating MHC I molecules, interfering with NK cell receptors, and using viral miRNAs. These mechanisms help viruses evade NK cell recognition and enhance their pathogenicity. Viruses such as influenza, hepatitis C, and cytomegalovirus (CMV) directly target NK cells or their receptors. For example, influenza virus can infect NK cells and induce apoptosis, while CMV encodes proteins that downregulate MHC I molecules and use MHC surrogates to avoid detection. HCMV also employs miRNAs to suppress MHC I expression, which helps it evade NK cell recognition. CMV is particularly adept at manipulating NK cell receptors, using MHC I surrogates like HLA-E and Qa-1 to mimic MHC I molecules and avoid detection. It also modulates NKG2D and Ly49 receptors, which are crucial for NK cell activation. Other viruses, such as flaviviruses, upregulate MHC I to avoid NK cell recognition, even though this makes them more susceptible to CD8+ T cell responses. Viruses also interfere with NK cell activation by blocking receptors or their ligands. For instance, HCMV targets NKG2D ligands and uses miRNAs to suppress their expression. Similarly, Kaposi's sarcoma-associated herpesvirus (KSHV) downregulates NKG2D ligands and NKp80 ligands to avoid NK cell-mediated lysis. NK cells can also acquire memory-like functions, which may enhance their ability to respond to viral infections. However, viruses have evolved strategies to counteract this, such as generating escape mutants that evade NK cell recognition. The interplay between NK cells and viruses highlights the ongoing evolutionary arms race, with viruses constantly adapting to evade immune detection while hosts develop mechanisms to combat viral infections.