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- W2165390070 abstract "HIV-1 viruses and virus-like particles (VLPs) bear nonnative junk forms of envelope (Env) glycoprotein that may undermine the development of antibody responses against functional gp120/gp41 trimers, thereby blunting the ability of particles to elicit neutralizing antibodies. Here, we sought to better understand the nature of junk Env with a view to devising strategies for its removal. Initial studies revealed that native trimers were surprisingly stable in the face of harsh conditions, suggesting that junk Env is unlikely to arise by trimer dissociation or gp120 shedding. Furthermore, the limited gp120 shedding that occurs immediately after synthesis of primary HIV-1 isolate Envs is not caused by aberrant cleavage at the tandem gp120/gp41 cleavage sites, which were found to cleave in a codependent manner. A major VLP contaminant was found to consist of an early, monomeric form of gp160 that is glycosylated in the endoplasmic reticulum (gp160ER) and then bypasses protein maturation and traffics directly into particles. gp160ER was found to bind two copies of monoclonal antibody (MAb) 2G12, consistent with its exclusively high-mannose glycan profile. These findings prompted us to evaluate enzyme digests as a way to remove aberrant Env. Remarkably, sequential glycosidase-protease digests led to a complete or near-complete removal of junk Env from many viral strains, leaving trimers and viral infectivity largely intact. Trimer VLPs may be useful neutralizing antibody immunogens." @default.
- W2165390070 created "2016-06-24" @default.
- W2165390070 creator A5023994515 @default.
- W2165390070 creator A5027151578 @default.
- W2165390070 creator A5036810091 @default.
- W2165390070 creator A5069640061 @default.
- W2165390070 date "2011-06-15" @default.
- W2165390070 modified "2023-10-13" @default.
- W2165390070 title "Enzyme Digests Eliminate Nonfunctional Env from HIV-1 Particle Surfaces, Leaving Native Env Trimers Intact and Viral Infectivity Unaffected" @default.
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- W2165390070 doi "https://doi.org/10.1128/jvi.00154-11" @default.
- W2165390070 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/3126298" @default.
- W2165390070 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/21471242" @default.
- W2165390070 hasPublicationYear "2011" @default.
- W2165390070 type Work @default.