Abstract
Integrases of different retroviruses assemble as functional complexes with varying multimers of the protein. Retroviral integrases require a divalent metal cation to perform one-step transesterification catalysis. Tetrameric prototype foamy virus (PFV) intasomes assembled from purified integrase and viral DNA oligonucleotides were characterized for their activity in the presence of different cations. While most retroviral integrases are inactive in calcium, PFV intasomes appear to be uniquely capable of catalysis in calcium. The PFV intasomes also contrast with other retroviral integrases by displaying an inverse correlation of activity with increasing manganese beginning at relatively low concentrations. The intasomes were found to be significantly more active in the presence of chloride co-ions compared to acetate. While HIV-1 integrase appears to commit to a target DNA within 20 s, PFV intasomes do not commit to target DNA during their reaction lifetime. Together, these data highlight the unique biochemical activities of PFV integrase compared to other retroviral integrases.
Highlights
Retroviruses require reverse transcription and integration to complete the viral life cycle [1]
prototype foamy virus (PFV) IN displayed an unexpected ability to perform strand transfer generating Half site integration (HSI) products with preprocessed viral cDNA ends (vDNA) in the presence of Ca. This suggested PFV IN can perform assembly and strand transfer in the presence of Ca, but not 30 processing. It was unclear whether intasomes would display similar results in the presence of these divalent metal ions, since PFV intasomes typically generate less HSI products compared to PFV IN
We show that PFV IN appears unique among retroviral Ins in the capacity to utilize calcium as a divalent cation for strand transfer
Summary
Retroviruses require reverse transcription and integration to complete the viral life cycle [1]. Human immunodeficiency virus (HIV-1) IN was characterized for its ability to assemble with vDNA, perform 30 processing, or catalyze strand transfer to a target DNA in the presence of Mn, Mg, Ca, cobalt (Co), or no cation [19]. This suggested PFV IN can perform assembly and strand transfer in the presence of Ca, but not 30 processing It was unclear whether intasomes would display similar results in the presence of these divalent metal ions, since PFV intasomes typically generate less HSI products compared to PFV IN. In spite of structural similarities among intasomes of different retroviruses, these enzymatic properties distinguish PFV IN from other retroviral INs
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