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The viral canyon
CORRESPONDENCE
The viral canyon From Michael G. Rossmann: I was happy to read in Jim Hogle’s [ l] recent review that the cryo-electron microscopic evidence [2] has convinced him that the ‘canyon’ is the receptor attachment site for rhino- and poliovirus. However, he states that “several investigators have questioned the rationale of (the) ‘Canyon Hypothesis’ ” on the basis of two arguments. What we had suggested [3,4] was that the receptor attachment site was hidden in the canyon, which is too narrow to permit binding of antibodies. Although amino acids within the canyon might be more conserved, thus maintaining their ability to bind to a much narrower, receptor, residues on the outer surface of the virion (where it has been shown that neutralizing epitopes bind) would be more variable, thus permitting the virus to escape the host’s immune surveillance. The relative conservation of the residues lining the canyon compared to the variability of residues on the outer viral surface were subsequently found to be consistent with this hypothesis [ 51. It was also established that the receptor was a thin molecule, as required by the canyon hypothesis, when the receptor for the major group of rhinoviruses was identified as the intercellular adhesion molecule-l (ICAMl) [6,7]. Now Hogle writes that “...the error-prone polymerases of RNA viruses produce. all possible mutations, including mutations in the receptor-binding sites. However, mutations that interfere with receptor binding are lethal and therefore not fixed in the virus population. Thus, the immune system can neither select for or against receptor-site mutations”. My original suggestion is dependent on the general evolutionary concept of the survival of the fittest. In this case, the fittest is the virus that is not recognized by the current antibodies being generated by the host. The molecular mechanism by which fitness can be achieved in a viral system is the rejection of those mutations that cause the recognition of a different receptor or inhibit recognition of any receptor. Thus, only those viruses survive as rhino- or as polio&uses which continue to be able to bind moderately well to the same receptor. At the same time, the rest of the viral surface is able to accept mutations. The surface changes help the virus to escape from the previously elicited neutralizing antibodies. Therefore, there is a real advantage for the virus to evolve rapidly
Current
Biology
in the vicinity of the external epitopes. Conversely, residues in the receptor attachment site must remain mostly the same. Hogle continues with a second possible reason for error in our original rationale. He points out that Acharya and co-workers [S] observe in foot-andmouth disease virus (FMDV) a conserved receptor attachment site (consisting of the amino-acid sequence RGD) surrounded by a region of variable residues. In FMDV, this site is far from hidden and is indeed on the very outside of the virus. Acharya et al. [8] propose an alternative mechanism for ‘hiding’ the receptor attachment site and Hogle [l] suggests that the same mechanism might apply to rhinoviruses. There may be more than one way of solving a problem in nature and what is the case for FMDV need not be true for rhinoviruses. Hogle does go on to suggest that the receptor may use the canyon to initiate conformational changes essential for cell entry. In this, as also in the rest of the review, I welcome his excellent survey of the subject. References 1.
2.
HOGLE JM: OLSON NH, MCCLELLAND rhinovirus
The viral canyon. Curr Biol 1993, 3:278-281. KOLUK.U PR, OLIVEIRA M& CHENG RH, GREVE JM, A, BAKER TS, ROSSMANN MG: Structure of a human complexed with its receptor molecule. Proc Nutl
Acad Sci USA 1993, 90:507-511. 3.
4.
5.
6.
7.
8.
ROSSNANN MG, ARNOLD E, ERICKSON JW, FRANKENBERGER FA, GRIFFITH JP, HECHT HJ, JOHNSON JE, KAIVIER G, Luo M, MOSSER AG, RUECKERT RR, SHERRY B, WEND G: Structure of a human common cold virus and functional relationship to other picornaviruses. Nature 1985, 317~145-153. RO~~MANN MG: The canyon hypothesis: hiding the host cell receptor attachment site on a viral surface from immune iurveilbnce. J Biol Chem 1989, 264:14587-14590. ROSSMANN MG, PALMENBERG AC: Conservation of the putative receptor attachment’ -‘Site in picomaviruses. Virology 1988, 164373-382. GREVE JM, DAVIS G, MEYER AM, FORTE CP, YOST SC, MAFUQR CW, KAMARCK ME, MCCLELLAND A The major human rhinovirus receptor is ICAM-1. Cell 1989, 568399847. STAUNTON DE, MERLUZZ VJ, ROTHLEIN R, BARTON R, MARLING SD, SPRINGER TA A cell adhesion molecule, ICAM-1, is the major surface receptor for rhmoviruses. Cell 1989, 563849-853. ACHARYA R, FRY E, STUART D, Fox G, ROWLWDS D, BROWN F: The three-dimensional structure of foot-and-mouth disease virns at 2.9k Nature 1989, 337:70%716.
Michael G. Rossmann, Department of Biological Sciences, Purdue University, West Lafayette, Indiana 47907-1392, USA.
1993,
Vol 3 No 8
The viral canyon From Michael G. Rossmann: I was happy to read in Jim Hogle’s [ l] recent review that the cryo-electron microscopic evidence [2] has convinced him that the ‘canyon’ is the receptor attachment site for rhino- and poliovirus. However, he states that “several investigators have questioned the rationale of (the) ‘Canyon Hypothesis’ ” on the basis of two arguments. What we had suggested [3,4] was that the receptor attachment site was hidden in the canyon, which is too narrow to permit binding of antibodies. Although amino acids within the canyon might be more conserved, thus maintaining their ability to bind to a much narrower, receptor, residues on the outer surface of the virion (where it has been shown that neutralizing epitopes bind) would be more variable, thus permitting the virus to escape the host’s immune surveillance. The relative conservation of the residues lining the canyon compared to the variability of residues on the outer viral surface were subsequently found to be consistent with this hypothesis [ 51. It was also established that the receptor was a thin molecule, as required by the canyon hypothesis, when the receptor for the major group of rhinoviruses was identified as the intercellular adhesion molecule-l (ICAMl) [6,7]. Now Hogle writes that “...the error-prone polymerases of RNA viruses produce. all possible mutations, including mutations in the receptor-binding sites. However, mutations that interfere with receptor binding are lethal and therefore not fixed in the virus population. Thus, the immune system can neither select for or against receptor-site mutations”. My original suggestion is dependent on the general evolutionary concept of the survival of the fittest. In this case, the fittest is the virus that is not recognized by the current antibodies being generated by the host. The molecular mechanism by which fitness can be achieved in a viral system is the rejection of those mutations that cause the recognition of a different receptor or inhibit recognition of any receptor. Thus, only those viruses survive as rhino- or as polio&uses which continue to be able to bind moderately well to the same receptor. At the same time, the rest of the viral surface is able to accept mutations. The surface changes help the virus to escape from the previously elicited neutralizing antibodies. Therefore, there is a real advantage for the virus to evolve rapidly
Current
Biology
in the vicinity of the external epitopes. Conversely, residues in the receptor attachment site must remain mostly the same. Hogle continues with a second possible reason for error in our original rationale. He points out that Acharya and co-workers [S] observe in foot-andmouth disease virus (FMDV) a conserved receptor attachment site (consisting of the amino-acid sequence RGD) surrounded by a region of variable residues. In FMDV, this site is far from hidden and is indeed on the very outside of the virus. Acharya et al. [8] propose an alternative mechanism for ‘hiding’ the receptor attachment site and Hogle [l] suggests that the same mechanism might apply to rhinoviruses. There may be more than one way of solving a problem in nature and what is the case for FMDV need not be true for rhinoviruses. Hogle does go on to suggest that the receptor may use the canyon to initiate conformational changes essential for cell entry. In this, as also in the rest of the review, I welcome his excellent survey of the subject. References 1.
2.
HOGLE JM: OLSON NH, MCCLELLAND rhinovirus
The viral canyon. Curr Biol 1993, 3:278-281. KOLUK.U PR, OLIVEIRA M& CHENG RH, GREVE JM, A, BAKER TS, ROSSMANN MG: Structure of a human complexed with its receptor molecule. Proc Nutl
Acad Sci USA 1993, 90:507-511. 3.
4.
5.
6.
7.
8.
ROSSNANN MG, ARNOLD E, ERICKSON JW, FRANKENBERGER FA, GRIFFITH JP, HECHT HJ, JOHNSON JE, KAIVIER G, Luo M, MOSSER AG, RUECKERT RR, SHERRY B, WEND G: Structure of a human common cold virus and functional relationship to other picornaviruses. Nature 1985, 317~145-153. RO~~MANN MG: The canyon hypothesis: hiding the host cell receptor attachment site on a viral surface from immune iurveilbnce. J Biol Chem 1989, 264:14587-14590. ROSSMANN MG, PALMENBERG AC: Conservation of the putative receptor attachment’ -‘Site in picomaviruses. Virology 1988, 164373-382. GREVE JM, DAVIS G, MEYER AM, FORTE CP, YOST SC, MAFUQR CW, KAMARCK ME, MCCLELLAND A The major human rhinovirus receptor is ICAM-1. Cell 1989, 568399847. STAUNTON DE, MERLUZZ VJ, ROTHLEIN R, BARTON R, MARLING SD, SPRINGER TA A cell adhesion molecule, ICAM-1, is the major surface receptor for rhmoviruses. Cell 1989, 563849-853. ACHARYA R, FRY E, STUART D, Fox G, ROWLWDS D, BROWN F: The three-dimensional structure of foot-and-mouth disease virns at 2.9k Nature 1989, 337:70%716.
Michael G. Rossmann, Department of Biological Sciences, Purdue University, West Lafayette, Indiana 47907-1392, USA.
1993,
Vol 3 No 8