Targeting cell surface HIV-1 Env protein to suppress infectious virus formation

Virus Res. 2017 May 2:235:33-36. doi: 10.1016/j.virusres.2017.04.003. Epub 2017 Apr 6.

Abstract

HIV-1 Env protein is essential for host cell entry, and targeting Env remains an important antiretroviral strategy. We previously found that a peptide triazole thiol KR13 and its gold nanoparticle conjugate AuNP-KR13 directly and irreversibly inactivate the virus by targeting the Env protein, leading to virus gp120 shedding, membrane disruption and p24 capsid protein release. Here, we examined the consequences of targeting cell-surface Env with the virus inactivators. We found that both agents led to formation of non-infectious virus from transiently transfected HEK293T cells. The budded non-infectious viruses lacked Env gp120 but contained gp41. Importantly, budded virions also retained the capsid protein p24, in stark contrast to p24 leakage from viruses directly treated by these agents and arguing that the agents led to deformed viruses by transforming the cells at a stage before virus budding. We found that the Env inactivators caused gp120 shedding from the transiently transfected HEK293T cells as well as non-producer CHO-K1-gp160 cells. Additionally, AuNP-KR13 was cytotoxic against the virus-producing HEK293T and CHO-K1-gp160 cells, but not untransfected HEK293T or unmodified CHO-K1 cells. The results obtained reinforce the argument that cell-surface HIV-1 Env is metastable, as on virus particles, and provides a conformationally vulnerable target for virus suppression and infectious cell inactivation.

Keywords: Gold nanoparticles; HIV-1; Infected cell inactivation; Multivalency; Peptide triazoles.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antiviral Agents / pharmacology*
  • CHO Cells
  • Cricetulus
  • HEK293 Cells
  • HIV-1 / physiology*
  • Humans
  • Peptides / pharmacology*
  • Triazoles / pharmacology*
  • Virus Assembly / drug effects*
  • Virus Inactivation*
  • env Gene Products, Human Immunodeficiency Virus / antagonists & inhibitors*

Substances

  • Antiviral Agents
  • Peptides
  • Triazoles
  • env Gene Products, Human Immunodeficiency Virus