HIV-1 uncoating is a poorly understood field and strengthening the idea behind this mechanism will add a strong base to the viral life cycle and interesting targets for antiviral therapy. Our previous work on the role of microtubules during HIV-1 uncoating has provided valuable information to the field of trafficking and HIV-1 uncoating. Our preliminary work supports a strong dependency of several microtubule associated proteins (MAPs) during HIV-1 uncoating and involvement of a variety of other host factors in this process. With this, we propose three specific aims to explore the role of these MAPs during HIV-1 uncoating.
Our first aim would be to decipher a mechanism by which these MAPs control viral uncoating. In the second aim, we would further characterize how the viral core trafficking is controlled by these MAPs and in the last aim, we would define the direct interactions between MAPs and the viral core which contribute to HIV-1 uncoating and trafficking. Our expertise and collaborations would help achieve these specific aims and show how the microtubule trafficking machinery plays an important role during HIV-1 uncoating. Findings from these proposed aims will provide critical understanding to the molecular interactions which drive HIV-1 uncoating and trafficking and would help identify better candidates for future antiviral therapy.

Public Health Relevance

The main purpose of this grant is to understand how the microtubule network of the host cell controls HIV-1 uncoating and trafficking. These are among the most poorly understood aspects of the viral lifecycle, and these studies will shed light on these topics that may reveal new opportunities for antiviral therapy.

National Institute of Health (NIH)
National Institute of Allergy and Infectious Diseases (NIAID)
Research Project (R01)
Project #
Application #
Study Section
Special Emphasis Panel (ZRG1)
Program Officer
Mcdonald, David Joseph
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Loyola University Chicago
Schools of Medicine
United States
Zip Code
Schulte, Bianca; Selyutina, Anastasia; Opp, Silvana et al. (2018) Localization to detergent-resistant membranes and HIV-1 core entry inhibition correlate with HIV-1 restriction by SERINC5. Virology 515:52-65
Martinez-Lopez, Alicia; Martin-Fernandez, Marta; Buta, Sofija et al. (2018) SAMHD1 deficient human monocytes autonomously trigger type I interferon. Mol Immunol 101:450-460
Dharan, Adarsh; Campbell, Edward M (2018) Role of Microtubules and Microtubule-Associated Proteins in HIV-1 Infection. J Virol 92:
Buffone, Cindy; Martinez-Lopez, Alicia; Fricke, Thomas et al. (2018) Nup153 Unlocks the Nuclear Pore Complex for HIV-1 Nuclear Translocation in Nondividing Cells. J Virol 92:
Opp, Silvana; Fricke, Thomas; Shepard, Caitlin et al. (2017) The small-molecule 3G11 inhibits HIV-1 reverse transcription. Chem Biol Drug Des 89:608-618
Dharan, Adarsh; Opp, Silvana; Abdel-Rahim, Omar et al. (2017) Bicaudal D2 facilitates the cytoplasmic trafficking and nuclear import of HIV-1 genomes during infection. Proc Natl Acad Sci U S A 114:E10707-E10716
Dharan, Adarsh; Talley, Sarah; Tripathi, Abhishek et al. (2016) KIF5B and Nup358 Cooperatively Mediate the Nuclear Import of HIV-1 during Infection. PLoS Pathog 12:e1005700