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Research papers (Caprisa)

Permanent URI for this collectionhttps://hdl.handle.net/10413/7816

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Browsing Research papers (Caprisa) by Author "Acharya, Priyamvada."

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    Structure and immune recognition of trimeric pre-fusion HIV-1 Env.
    (Macmillan Publishers Limited., 2014) Pancera, Marie.; Zhou, Tongqing.; Druz, Aliaksandr.; Georgiev, Ivelin S.; Soto, Cinque.; Gorman, Jason.; Huang, Jinghe.; Acharya, Priyamvada.; Chuang, Gwo-Yu.; Ofek, Gilad.; Stewart-Jones, Guillaume B. E.; Stuckey, Jonathan.; Bailer, Robert T.; Joyce, M. Gordon.; Louder, Mark K.; Tumba, Nancy Lola.; Yang, Yongping.; Zhang, Baoshan.; Cohen, Myron S.; Haynes, Barton F.; Mascola, John R.; Morris, Lynn.; Munro, James B.; Blanchard, Scott C.; Mothes, Walther.; Connors, Mark.; Kwong, Peter D.
    The human immunodeficiency virus type 1 (HIV-1) envelope (Env) spike, comprising three gp120 and three gp41 subunits, is a conformational machine that facilitates HIV-1 entry by rearranging from a mature unliganded state, through receptor-bound intermediates, to a post-fusion state. As the sole viral antigen on the HIV-1 virion surface, Env is both the target of neutralizing antibodies and a focus of vaccine efforts. Here we report the structure at 3.5 Å resolution for an HIV-1 Env trimer captured in a mature closed state by antibodies PGT122 and 35O22. This structure reveals the pre-fusion conformation of gp41, indicates rearrangements needed for fusion activation, and defines parameters of immune evasion and immune recognition. Pre-fusion gp41 encircles amino- and carboxy-terminal strands of gp120 with four helices that form a membrane-proximal collar, fastened by insertion of a fusion peptide-proximal methionine into a gp41-tryptophan clasp. Spike rearrangements required for entry involve opening the clasp and expelling the termini. N-linked glycosylation and sequence-variable regions cover the pre-fusion closed spike; we used chronic cohorts to map the prevalence and location of effective HIV-1-neutralizing responses, which were distinguished by their recognition of N-linked glycan and tolerance for epitope-sequence variation.