Dr Krishan K Pandey is the author of HIV-1 Integrase Strand Transfer Inhibitors: Novel Insights into their Mechanism of Action, which was recently published in Retrovirology: Research and Treatment. In this interview Dr Pandey discusses his research, recently published articles and his views on open access publishing.

The Editor in Chief of Retrovirology: Research and Treatment recently issued a call for papers.

What is the primary focus of your research?

We utilize various biochemical and biophysical tools to investigate the mechanisms associated with retroviral integration. We are investigating the mode of action of integrase strand transfer inhibitors including Raltegravir and development of drug resistance in HIV-1.

What are the most exciting developments arising from current research in your area?

Recently, we identified the synaptic complex, a transient intermediate in the HIV-1 concerted integration pathway in vitro. In the synaptic complex, the two viral DNA ends are juxtaposed by integrase non-covalently. Upon binding a target DNA, the synaptic complex produces the strand transfer complex, the terminal nucleoprotein product in the concerted integration pathway. We resolve these complexes by native agarose gel electrophoresis. We also determined that most integrase strand transfer inhibitors prevent the conversion of synaptic complex to strand transfer complex by inhibiting the binding of target DNA to synaptic complex, possibly by modifying viral DNA binding.

Who are your main collaborators? Please describe your work with them.

We have been collaborating with Merck & Co over several years and have investigated integrase inhibitors developed by Merck. In 2007, Raltegravir produced by Merck, became the first integrase inhibitor approved by the FDA for treatment of HIV-1 infections.

How did you come to be working in your research area?

I work in the laboratory of Dr. Duane Grandgenett and currently hold a Faculty Research Associate position.

What do you think about the development of open access publishing?

Open access publishing is important for the scientific community because it delivers the most recent knowledge to a much broader audience.

What articles and/or books have you published recently?

• Pandey KK, Sinha S, Grandgenett DP (2007). Transcriptional coactivator LEDGF/p75 modulates human immunodeficiency virus type 1 integrase-mediated concerted integration. J Virol 81(8): 3969-3979.

• Pandey KK, Bera S, Zahm J, Vora A, Stillmock K, Hazuda D, Grandgenett DP (2007). Inhibition of human immunodeficiency virus type 1 concerted integration by strand transfer inhibitors which recognize a transient structural intermediate. J Virol 81(22): 12189-12199.

• Zahm JA, Bera S, Pandey KK, Vora A, Stillmock K, Hazuda D, Grandgenett DP (2008). Mechanisms of human immunodeficiency virus type 1 concerted integration related to strand transfer inhibition and drug resistance. Antimicrob Agents Chemother 52(9): 3358-3368.

• Grandgenett DP, Bera S, Pandey KK, Vora AC, Zahm J, Sinha S (2009). Biochemical and biophysical analyses of concerted (U5/U3) integration. Methods 47(4): 229-236.

• Bera S, Pandey KK, Vora AC, Grandgenett DP (2009). Molecular interactions between HIV-1 integrase and the two viral DNA ends within the synaptic complex that mediates concerted integration. J Mol Biol 389(1): 183-198.

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