Discipline: Biological Sciences
Subcategory: Microbiology/Immunology/Virology
Elizabeth Helen Quaye - University at Buffalo
Co-Author(s): Rakesh Kumar Sharma, Univerity of Delhi, Delhi, India; Katherine Cwiklinski, University at Bufalo, Buffalo, NY; Ravikumar Aalinkeel, University at Bufalo, Buffalo, NY; Jessica L. Reynolds, University at Bufalo, Buffalo, NY; Donald E . Sykes, University at Bufalo, Buffalo, NY; Supriya D. Mahajan University at Bufalo, Buffalo, NY; and Stanley A Schwartz University at Bufalo, Buffalo, NY
Silver nanoparticles (AgNPs) have been demonstrated to have antiviral properties and thus could be used as agents against human immunodeficiency virus (HIV). The pathogenic potential of HIV-1 is due to its rapid replication, spread and successful neutralization of host restriction factors which is mediated by its regulatory and accessory proteins. Curcumin has anti-HIV activity as it is an inhibitor of HIV-1 protease, integrase and LTR. Further, it also inhibits NF-κB pathway which is important for HIV-1 gene expression. A nanoformulation of curcumin and AgNPs, (Cur-AgNPs) will allow increased bioavailability of curcumin and should have excellent anti-HIV activity. We synthesized and characterized Cur-AgNPs and found them to be 45nm by dynamic light scattering with a maximum absorbance at 406 nm. The antiretroviral effects of Cur-AgNP were determined in ACH-2 cells latently infected with HIV-1. ACH-2 cells, were treated with Cur-AgNP for 24-48 hr. Expression of HIV-1 LTR and p24, the pro-inflammatory cytokines, IL-1, TNF-, and NF-κB were quantitated. Treatment of ACH-2 cells—latently infected with HIV-1—with Cur-AgNP produced no toxic effects but significantly inhibited the expression of: HIV-1 LTR (-73%, p<0.01) and p24 (-57%, p<0.05), IL-1(-61%, p<0.01), TNF-(-54%, p<0.05), IL-6 (-68%, p<0.01), and NF-κB (-79%, p<0.0001) as compared to untreated controls. Thus, Cur-AgNP have therapeutic potential as direct antiretroviral agents, as well as immunomodulatory activities inhibiting the expression of pro-inflammatory mediators induced by infection with HIV-1. Experimental controls, such as AgNP alone, curcumin alone and conventional silver nanoparticles capped with citric acid produced no similar biological effects. We conclude that treatment of HIV-1 infected cells with Cur-AgNP, significantly reduced replication of HIV by inhibition of NF-κB nuclear translocation and the downstream expression of the pro-inflammatory cytokines IL-1β, TNF- and IL-6. Subsequent in vivo studies with Cur-AgNP using a humanized mouse model of HIV infection are underway.
Not SubmittedFunder Acknowledgement(s): The authors would like to acknowledge the funding support from the Cameron Troup Fund, administered by the Kaleida Health Foundation, Buffalo, NY awarded to Dr. Stanley A Schwartz. Dr. Rakesh Kumar Sharma is the recipient of the Raman Post-doctoral Fellowship award and would like acknowledge from the University Grants Commission, Government of India and the University of Delhi, for their generous support.
Faculty Advisor: Dr. Supriya Mahajan, smahajan@buffalo.edu
Role: My job consisted of synthesizing the silver nanoparticles loaded with curcumin. I also did RTqPCR work with the nanoparticles and analyzed the data.