The invention provides an isolated nucleic acid encoding a TRIM—cyclophilin A fusion sequence encoding a TRIMcyp fusion protein which is active as an anti-viral agent, and in particular an anti-HIV-1 agent. The invention provides for a nucleic acid encoding a polypeptide having both TRIM activity and cyclophilin activity. The invention provides for an isolated polynucleotide encoding a TRIM-cyclophilin fusion protein, or variants thereof retaining the TRIM and cyclophilin activities. The invention provides for compositions thereof, antibodies that specifically bind thereto, and vectors and host cells comprising the nucleic acid or polypeptide. In addition, the invention provides for methods for treating or preventing viral infection, or reducing viral load in a subject comprising administering the nucleic acid, polypeptide, vector, or composition to the subject in an amount effective to treat or prevent the viral infection. In some embodiments, the viral infection is HIV-1 infection, hepatitis C infection, pox virus infection, vaccinia virus infection, or HTLV infection.