Envelope proteins containing single amino acid substitutions support a structural model of the receptor-binding domain of bovine leukemia virus surface protein

Elizabeth R. Johnston, Lorraine Albritton, Kathryn Radke

Research output: Contribution to journalArticle

33 Citations (Scopus)

Abstract

Functional domains of the strikingly conserved envelope (Env) glycoproteins of bovine leukemia virus (BLV) and its close relative, human T-cell leukemia virus type 1 (HTLV-1), are still being defined. We have used BLV Env protein variants to gain insights into the structure and function of this important determinant of viral infectivity. Each of 23 different single amino acid variants found in cDNA clones of env transcripts present after short-term culture of peripheral blood mononuclear cells from BLV-infected sheep was expressed in COS-1 cells and tested for the ability to mediate cell fusion and to be cleaved to surface (SU) and transmembrane (TM) protein subunits. Of 11 Env variants that failed to induce syncytia or did so poorly, 7 contained changes in amino acids identical or chemically conserved in the HTLV-1 Env protein. These seven included the four variants that showed aberrant proteolytic cleavage and poor cell surface expression, underscoring their importance for Env structure. Ten of 12 variants that retained wild-type syncytium-inducing ability clustered in the N-terminal hall of BLV SU, which forms the putative receptor-binding domain (RBD). Several variants in the RBD showed evidence of subtle misfolding, as judged by reduced binding to monoclonal antibodies recognizing conformational epitopes F, G, and H formed by the N terminus of SU. We modeled the BLV RBD by aligning putative structural elements with known elements of the ecotropic Friend murine leukemia virus RBD monomer. All the variant RBD residues but one are exposed on the surface of this BLV model. These variants as well as function-altering, antibody-reactive residues defined by other investigators group on one face of the molecular model. They are strikingly absent from the opposite face, implying that it is likely to face inward in Env complexes. This surface might interact with the C-terminal domain of SU or with an adjacent monomer in the Env oligomer. This location suggests an orientation for the monomer of ecotropic Friend murine leukemia virus RBD.

Original languageEnglish (US)
Pages (from-to)10861-10872
Number of pages12
JournalJournal of Virology
Volume76
Issue number21
DOIs
StatePublished - Nov 1 2002

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Bovine Leukemia Virus
Bovine leukemia virus
Structural Models
surface proteins
amino acid substitution
Amino Acid Substitution
Membrane Proteins
Virus Attachment
receptors
Friend murine leukemia virus
Viral Envelope Proteins
Deltaretrovirus
Murine leukemia virus
Giant Cells
Proteins
proteins
giant cells
Amino Acids
Molecular Models
Cell Fusion

All Science Journal Classification (ASJC) codes

  • Immunology

Cite this

Envelope proteins containing single amino acid substitutions support a structural model of the receptor-binding domain of bovine leukemia virus surface protein. / Johnston, Elizabeth R.; Albritton, Lorraine; Radke, Kathryn.

In: Journal of Virology, Vol. 76, No. 21, 01.11.2002, p. 10861-10872.

Research output: Contribution to journalArticle

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