The present invention includes compositions and methods of inhibiting or activating TLR7 signaling. In one aspect, a composition includes an inhibitor of TLR7 signaling is described, where the inhibitor of TLR7 signaling is a TLR7 inhibitory oligonucleotide, a TLR7 antibody, or a TLR7 antagonist. In another aspect, a composition and method are described for preventing and treating viral infection of a T cell in a subject. Methods for decreasing T cell proliferation by administering a composition with a TLR7 ligand or agonist or inducing T cell anergy in a subject by stimulating T cells with a TLR7 ligand or agonist are also described.