The glycosylated-PEG-oHSV exhibited remarkable features, including tumor-specific targeting, enhanced cell infection ability, reduced brain infection with minimized side effects, flexibility and small size, reduced host antiviral response and Tregs in the tumor microenvironment, and increased infiltration of IFN-γ+CD8+T cells and NK cells into tumors after systemic administration. Here, CD8A is linked to infection.