Scholarlink

<p>Henipaviruses, in the <i>Paramyxoviridae</i> family, includes the highly virulent Nipah virus that causes reoccurring outbreaks of deadly disease. Recent discoveries of <i>Henipavirus</i>-like species, including the zoonotic Langya virus, have revealed much higher antigenic diversity than currently characterized and prompted the reorganization of these viruses into the <i>Henipavirus</i> and <i>Parahenipavirus</i> genera. Here, to explore the limits of structural and antigenic variation in both genera, collectively referred to as HNVs, we construct an expanded, diverse panel of HNV fusion and attachment glycoproteins from non-redundant HNV strains that better reflect global HNV diversity. We express and purify the fusion protein ectodomains and the attachment protein head domains and study their biochemical and biophysical properties. We perform immunization experiments in mice, eliciting antibodies reactive to multiple HNV fusion proteins. Cryo-electron microscopy structures elucidate molecular determinants of differential pre-fusion state stability and higher order contacts. A crystal structure of the Gamak virus attachment head domain reveals an additional domain appended to the conserved 6-bladed, β-propeller fold. Taken together, these studies expand the known structural and antigenic limits of the HNVs, reveal cross-reactive epitopes within both genera and provide foundational data for the development of broadly reactive countermeasures.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

Mechanistic and antigenic boundaries of Henipavirus and Parahenipavirus glycoproteins

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年6月19日

查看全文
  • Aaron J. May,
  • Muralikrishna Lella,
  • Jared Lindenberger,
  • Alex Berkman,
  • Ujjwal Kumar,
  • Kejun Liu,
  • Moumita Dutta,
  • Maggie Barr,
  • Rob Parks,
  • Xiaozhi Lu,
  • Madison Berry,
  • Amanda Powell,
  • Amelia G. Thompson,
  • Sravya Sowdamini Nakka,
  • Camila T. França,
  • Xiao Huang,
  • Arpita Mrigwani,
  • Kijun Song,
  • Victor Ilevbare,
  • Salam Sammour,
  • Chan Soo Park,
  • Radha Devkota Adhikari,
  • Priyanka Devkota,
  • Katarzyna Janowska,
  • Yanshun Liu,
  • Garrett Scapellato,
  • Taylor N. Spence,
  • Katayoun Mansouri,
  • Kevin Wiehe,
  • Nancy J. Sullivan,
  • Rosemarie Mason,
  • Robert J. Edwards,
  • Kevin O. Saunders,
  • Barton F. Haynes,
  • Priyamvada Acharya

摘要

Henipaviruses, in the Paramyxoviridae family, includes the highly virulent Nipah virus that causes reoccurring outbreaks of deadly disease. Recent discoveries of Henipavirus-like species, including the zoonotic Langya virus, have revealed much higher antigenic diversity than currently characterized and prompted the reorganization of these viruses into the Henipavirus and Parahenipavirus genera. Here, to explore the limits of structural and antigenic variation in both genera, collectively referred to as HNVs, we construct an expanded, diverse panel of HNV fusion and attachment glycoproteins from non-redundant HNV strains that better reflect global HNV diversity. We express and purify the fusion protein ectodomains and the attachment protein head domains and study their biochemical and biophysical properties. We perform immunization experiments in mice, eliciting antibodies reactive to multiple HNV fusion proteins. Cryo-electron microscopy structures elucidate molecular determinants of differential pre-fusion state stability and higher order contacts. A crystal structure of the Gamak virus attachment head domain reveals an additional domain appended to the conserved 6-bladed, β-propeller fold. Taken together, these studies expand the known structural and antigenic limits of the HNVs, reveal cross-reactive epitopes within both genera and provide foundational data for the development of broadly reactive countermeasures.