Critical role of leucine-valine change in distinct low pH requirements for membrane fusion between two related retrovirus envelopes

Marceline Côté, Yi Min Zheng, Kun Li, Shi-Hua Xiang, Lorraine M. Albritton, Shan Lu Liu

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

Many viruses use a pH-dependent pathway for fusion with host cell membrane, the mechanism of which is still poorly understood. Here we report that a subtle leucine (Leu)-valine (Val) change at position 501 in the envelope glycoproteins (Envs) of two related retroviruses, jaagsiekte sheep retrovirus (JSRV) and enzootic nasal tumor virus (ENTV), is responsible for their distinct low pH requirements for membrane fusion and infection. The Leu and Val residues are predicted to reside within the C-terminal heptad repeat (HR2) region of JSRV and ENTV Envs, particularly proximal to the hairpin turn of the putative six-helix bundle (6HB). Substitution of the JSRV Leu with a Val blocked the Env-mediated membrane fusion at pH 5.0, whereas replacement of the ENTV Val with a Leu rendered the ENTV Env capable of fusing at pH 5.0.ALeu-Val change has no apparent effect on the stability of native Env, but appears to stabilize an intermediate induced by receptor binding. These results are consistent with the existence of at least two metastable conformations of these viral glycoproteins, the native prefusion conformation and a receptor-induced metastable intermediate. Collectively, this work represents an interesting perhaps unique example whereby a simple Leu-Val change has critical impact on pH-dependent virus fusion and entry.

Original languageEnglish (US)
Pages (from-to)7640-7651
Number of pages12
JournalJournal of Biological Chemistry
Volume287
Issue number10
DOIs
StatePublished - Mar 2 2012

Fingerprint

Membrane Fusion
Valine
Retroviridae
Viruses
Leucine
Jaagsiekte sheep retrovirus
Oncogenic Viruses
Fusion reactions
Membranes
Nose
Tumors
Conformations
env Gene Products
Virus Internalization
Terminal Repeat Sequences
Cell membranes
Glycoproteins
Substitution reactions
Cell Membrane
Infection

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Molecular Biology

Cite this

Critical role of leucine-valine change in distinct low pH requirements for membrane fusion between two related retrovirus envelopes. / Côté, Marceline; Zheng, Yi Min; Li, Kun; Xiang, Shi-Hua; Albritton, Lorraine M.; Liu, Shan Lu.

In: Journal of Biological Chemistry, Vol. 287, No. 10, 02.03.2012, p. 7640-7651.

Research output: Contribution to journalArticle

Côté, Marceline ; Zheng, Yi Min ; Li, Kun ; Xiang, Shi-Hua ; Albritton, Lorraine M. ; Liu, Shan Lu. / Critical role of leucine-valine change in distinct low pH requirements for membrane fusion between two related retrovirus envelopes. In: Journal of Biological Chemistry. 2012 ; Vol. 287, No. 10. pp. 7640-7651.
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