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Targeting cell surface HIV-1 Env protein to suppress infectious virus formation
Arangassery Rosemary Bastian1, Charles G Ang1, Kantharaju Kamanna2
1Biochemistry and Molecular Biology, Drexel University College of Medicine, Philadelphia, PA 19102, United States; School of Biomedical Engineering, Science and Health Systems, Drexel University, Philadelphia, PA 19104, United States.
Virus Research
|April 10, 2017
Summary
New HIV-1 treatments targeting the Env protein inactivate the virus and prevent infection. These agents cause virus shedding and cell transformation, leading to non-infectious viral particles and reduced infectivity.
Area of Science:
- Virology
- Immunology
- Materials Science
Background:
- The Human Immunodeficiency Virus type 1 (HIV-1) Env protein is critical for viral entry into host cells.
- Targeting the Env protein is a key strategy in developing antiretroviral therapies.
- Previous research identified peptide triazole thiol KR13 and its gold nanoparticle conjugate AuNP-KR13 as direct HIV-1 inactivators.
Purpose of the Study:
- To investigate the effects of targeting cell-surface HIV-1 Env with virus inactivators KR13 and AuNP-KR13.
- To determine the impact of these agents on virus production and cell viability.
Main Methods:
- Transient transfection of HEK293T cells and use of non-producer CHO-K1-gp160 cells.
- Treatment of cells and virus particles with KR13 and AuNP-KR13.
- Analysis of viral components (Env gp120, gp41, p24 capsid protein) in cell-free virions and cell cultures.
- Cytotoxicity assays for AuNP-KR13.
Main Results:
- Both KR13 and AuNP-KR13 treatment resulted in the formation of non-infectious, budded viruses from transfected cells.
- These non-infectious viruses lacked Env gp120 but contained gp41 and retained the p24 capsid protein, indicating deformed virion formation.
- The agents induced gp120 shedding from cell surfaces and AuNP-KR13 exhibited cytotoxicity against virus-producing cells.
Conclusions:
- Cell-surface HIV-1 Env is a metastable and conformationally vulnerable target.
- Targeting cell-surface Env with inactivators like KR13 and AuNP-KR13 offers a promising strategy for virus suppression and inactivation of infectious cells.