Prototype foamy virus integrase is promiscuous for target choice

• Published in: Biochemical and biophysical research communications 2018-09, Vol.503 (3), p.1241-1246
• Main Authors: Mackler, R.M., Lopez, M.A., Osterhage, M.J., Yoder, K.E.
• Format: Article
• Language: English
• Subjects: 60 APPLIED LIFE SCIENCES; AIDS VIRUS; CALCIUM; Divalent cation; DNA; DNA, Viral - genetics; DNA, Viral - metabolism; Enzymology; HIV-1 - enzymology; Integrase; Integrases - isolation & purification; Integrases - metabolism; PROTEINS; Prototype foamy virus; Retrovirus; Spumavirus - enzymology; Substrate Specificity
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1016/j.bbrc.2018.07.031

Retroviruses have two essential activities: reverse transcription and integration. The viral protein integrase (IN) covalently joins the viral cDNA genome to the host DNA. Prototype foamy virus (PFV) IN has become a model of retroviral intasome structure. However, this retroviral IN has not been well-characterized biochemically. Here we compare PFV IN to previously reported HIV-1 IN activities and discover significant differences. PFV IN is able to utilize the divalent cation calcium during strand transfer while HIV-1 IN is not. HIV-1 IN was shown to completely commit to a target DNA within 1 min, while PFV IN is not fully committed after 60 min. These results suggest that PFV IN is more promiscuous compared to HIV-1 IN in terms of divalent cation and target commitment. •PFV IN is able to utilize calcium as the divalent cation for strand transfer, but not 3’ end processing.•PFV IN does not commit to a target DNA within 60 minutes.•The PFV integration sequence preference does not enhance nor inhibit integration.