Your browser doesn't support javascript.
loading
Conformational flexibility of HIV-1 envelope glycoproteins modulates transmitted/founder sensitivity to broadly neutralizing antibodies.
Parthasarathy, Durgadevi; Pothula, Karunakar Reddy; Ratnapriya, Sneha; Cervera Benet, Héctor; Parsons, Ruth; Huang, Xiao; Sammour, Salam; Janowska, Katarzyna; Harris, Miranda; Sodroski, Joseph; Acharya, Priyamvada; Herschhorn, Alon.
Afiliación
  • Parthasarathy D; Division of Infectious Diseases and International Medicine, Department of Medicine, University of Minnesota, Minneapolis, MN, USA.
  • Pothula KR; Duke Human Vaccine Institute, Duke University, Durham, NC, USA.
  • Ratnapriya S; Division of Infectious Diseases and International Medicine, Department of Medicine, University of Minnesota, Minneapolis, MN, USA.
  • Cervera Benet H; Division of Infectious Diseases and International Medicine, Department of Medicine, University of Minnesota, Minneapolis, MN, USA.
  • Parsons R; Duke Human Vaccine Institute, Duke University, Durham, NC, USA.
  • Huang X; Department of Biochemistry, Duke University, Durham, NC, USA.
  • Sammour S; Duke Human Vaccine Institute, Duke University, Durham, NC, USA.
  • Janowska K; Duke Human Vaccine Institute, Duke University, Durham, NC, USA.
  • Harris M; Duke Human Vaccine Institute, Duke University, Durham, NC, USA.
  • Sodroski J; Division of Infectious Diseases and International Medicine, Department of Medicine, University of Minnesota, Minneapolis, MN, USA.
  • Acharya P; Department of Cancer Immunology and Virology, Dana-Farber Cancer Institute, Boston, MA, USA.
  • Herschhorn A; Department of Microbiology, Harvard Medical School, Boston, MA, USA.
Nat Commun ; 15(1): 7334, 2024 Aug 26.
Article en En | MEDLINE | ID: mdl-39187497
ABSTRACT
HIV-1 envelope glycoproteins (Envs) of most primary HIV-1 strains exist in closed conformation and infrequently sample open states, limiting access to internal epitopes. Thus, immunogen design aims to mimic the closed Env conformation as preferred target for eliciting broadly neutralizing antibodies (bnAbs). Here we identify incompletely closed Env conformations of 6 out of 13 transmitted/founder (T/F) strains that are sensitive to antibodies that recognize internal epitopes typically exposed on open Envs. A 3.6 Å cryo-electron microscopy structure of unliganded, incompletely closed T/F Envs (1059-SOSIP) reveals protomer motion that increased sampling of states with incompletely closed trimer apex. We reconstruct de novo the post-transmission evolutionary pathway of a second T/F. Evolved viruses exhibit increased Env resistance to cold, soluble CD4 and 19b, all of which correlate with closing of the adapted Env trimer. Lastly, we show that the ultra-broad N6 bnAb efficiently recognizes different Env conformations and exhibits improved antiviral breadth against VRC01-resistant Envs isolated during the first-in-humans antibody-mediated-prevention trial.
Asunto(s)
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Conformación Proteica / Anticuerpos Anti-VIH / VIH-1 / Microscopía por Crioelectrón / Productos del Gen env del Virus de la Inmunodeficiencia Humana / Anticuerpos Neutralizantes Límite: Humans Idioma: En Revista: Nat Commun Asunto de la revista: BIOLOGIA / CIENCIA Año: 2024 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Reino Unido
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Conformación Proteica / Anticuerpos Anti-VIH / VIH-1 / Microscopía por Crioelectrón / Productos del Gen env del Virus de la Inmunodeficiencia Humana / Anticuerpos Neutralizantes Límite: Humans Idioma: En Revista: Nat Commun Asunto de la revista: BIOLOGIA / CIENCIA Año: 2024 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Reino Unido