Identification of a critical basic residue on the ecotropic murine leukemia virus receptor

Zhaohui Qian, Robin Donald, Hongzhe Wang, Qianmin Chen, Lorraine Albritton

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

Susceptibility to ecotropic murine leukemia viruses (MLV) is restricted to mice and rats at the level of virus binding to the host cell receptor. Asparagine 232, valine 233, tyrosine 235, and glutamic acid 237 in the third extracellular domain (EL3) of the receptor are critical determinants of the host range difference between mice and humans. However, placing these residues in the human homolog confers only partial binding, indicating that other divergent sequences are involved. We sought to determine if the other sequences lie within or outside EL3. Here we report the identification of lysine 234 as another critical residue that influences virus binding and infection, as well as evidence that the unidentified sequences lie outside EL3. Each of the four basic residues in the third extracellular domain were changed to an acidic residue and initially examined in combination with a change at position 235 or position 237. Substitution of lysine 211, 215, or 222 combined with substitution of the critical tyrosine 235 or glutamic acid 237 did not affect virus infection. However, combined substitution of lysine 234, a conserved residue between mice and humans, and tyrosine 235 resulted in a marked decrease in virus infection and binding. A lysine 234 change alone reduced virus binding, contrary to previous observations that at least two of the other four residues must be changed before binding is reduced. Interestingly, there was no decrease in infection when lysine 234 was replaced in combination with glutamic acid 237. This result suggests that residue 234 may act by influencing the local structure of residues 233 to 235, whereas the presence of a glycine at position 236 may prevent this influence from extending to residue 237. With this report, the involvement of all the residues divergent between mice and humans in the third extracellular domain has been ruled out, suggesting that as yet unidentified determinants lie in other extracellular domains.

Original languageEnglish (US)
Pages (from-to)8596-8601
Number of pages6
JournalJournal of Virology
Volume77
Issue number15
DOIs
StatePublished - Aug 1 2003

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Murine leukemia virus
Virus Attachment
Lysine
lysine
Virus Diseases
viruses
glutamic acid
Tyrosine
tyrosine
Glutamic Acid
mice
infection
Murine Leukemia Viruses
receptors
Host Specificity
Asparagine
Valine
asparagine
valine
glycine (amino acid)

All Science Journal Classification (ASJC) codes

  • Immunology

Cite this

Identification of a critical basic residue on the ecotropic murine leukemia virus receptor. / Qian, Zhaohui; Donald, Robin; Wang, Hongzhe; Chen, Qianmin; Albritton, Lorraine.

In: Journal of Virology, Vol. 77, No. 15, 01.08.2003, p. 8596-8601.

Research output: Contribution to journalArticle

Qian, Zhaohui ; Donald, Robin ; Wang, Hongzhe ; Chen, Qianmin ; Albritton, Lorraine. / Identification of a critical basic residue on the ecotropic murine leukemia virus receptor. In: Journal of Virology. 2003 ; Vol. 77, No. 15. pp. 8596-8601.
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