Yiyao Wang, Youqin Zeng, Hao Zhou
Lactate is an important metabolic byproduct that regulates protein function under diverse physiological and pathological conditions. Protein lactylation has emerged as a critical regulatory mechanism in virus-host interactions. Lactylation reshapes the tRNA regulatory system during Kaposi's sarcoma-associated herpesvirus (KSHV) infection and modulates the mRNA processing machinery to regulate host antiviral immunity during severe fever with thrombocytopenia syndrome virus (SFTSV) infection. In addition, lactylation also regulates telomere maintenance during human papillomavirus (HPV) and hepatitis B virus (HBV) infections. Although an increasing number of studies has revealed have clarified the involvement of protein lactylation during viral infections, a systematic understanding of the interplay of lactylation between host immunity and viral evasion is currently lacking. Herein, we summarize the most recent advances and emerging discoveries regarding the role of protein lactylation in regulating host immunity and cellular responses to lactate during viral infections. We further discuss the mechanistic crosstalk between lactylation and other signaling networks, aiming to broaden the current perspective of lactylation-mediated regulation in viral pathogenesis, ultimately emphasizing this modification as an emerging target for antiviral interventions.