The paper by Tio et al presents an interesting analysis of dengue binding proteins expressed by PS Clone D ( a porcine kidney cell line), that provides substantial support of our proposal that the 37/67kDa high affinity laminin receptor is a dengue virus receptor protein.
It is a shame therefore that the authors both blur the demarcation between a “binding protein” and a “receptor protein” as well as misrepresent our previous studies.
Specifically, the authors state that (Introduction, Page 3, lines 14 to 17) …
“Moreover specifically, mass spectroscopic methods have been used to identify reactive bands using VOPBA and it has been suggested that DENV-2 interacts with GRP78 [15] while DENV-1 interacts with the 37k/67kDa high affinity laminin receptor [16]”
And also that (Discussion, Page 7, lines 7 to 9)
“The laminin receptor has already been described as a receptor for DENV-1 by single dimension VOPBA followed by MS/MS [16]”
Neither of these statements are correct. In the two studies cited, in both cases VOPBA and MS/MS were used to identify candidate binding proteins. The assignment of the two proteins as dengue virus receptors came after functional studies using antibodies directed against the respective proteins to inhibit dengue virus internalization. In the case of the 37/67kDa high affinity laminin receptor protein inhibition was additionally observed in the presence of a natural ligand for this receptor (laminin) and down regulation of the protein was seen in response to infection. In each case ALL serotypes were functionally examined for inhibition effects (although this is not presented in the GRP78/Bip manuscript) and, as stated, the effects were serotype specific.
Additionally the statement that “(Discussion, Page 8, lines 6 to 8):
“ Contrary to earlier suggestions that LAMR1 is a DENV-1 specific receptor protein [14, 16], in our hands, DENV-1, DENV-2 and DENV-3 were all shown to interact with the same molecule LAMR1 although DENV-4 did not”
is also wrong as the authors have confused the ability of the various serotypes to interact (bind) with the 37/67kDa high affinity laminin receptor protein (their study) and the ability of the various serotypes to use the protein as a receptor (our studies).
Moreover the assumption that the HepG2 and PS Clone D are in some way functionally equivalent, and that what is found in one cell line must be correct for others is somewhat simplistic. The simple fact that DC-SIGN has been shown to be a functional receptor for dendritic cells, HSP 70 and 90 for U937 cells (Journal of Virology Apr 2005, 4557-4567) while our group has identified other binding/receptor proteins in other cell types would suggest that the interaction between specific dengue viruses and specific cell types is likely to be highly complex. Lastly, given that the Cardosa study identifies the same protein as a dengue virus binding protein that we have characterized as a dengue virus receptor protein, it is unfortunate that the authors did not seek to keep the nomenclature of this protein the same to avoid future confusion.
Virology Journal
Binding protein as opposed to receptor protein
15 February 2006
The paper by Tio et al presents an interesting analysis of dengue binding proteins expressed by PS Clone D ( a porcine kidney cell line), that provides substantial support of our proposal that the 37/67kDa high affinity laminin receptor is a dengue virus receptor protein.
It is a shame therefore that the authors both blur the demarcation between a “binding protein” and a “receptor protein” as well as misrepresent our previous studies.
Specifically, the authors state that (Introduction, Page 3, lines 14 to 17) …
“Moreover specifically, mass spectroscopic methods have been used to identify reactive bands using VOPBA and it has been suggested that DENV-2 interacts with GRP78 [15] while DENV-1 interacts with the 37k/67kDa high affinity laminin receptor [16]”
And also that (Discussion, Page 7, lines 7 to 9)
“The laminin receptor has already been described as a receptor for DENV-1 by single dimension VOPBA followed by MS/MS [16]”
Neither of these statements are correct. In the two studies cited, in both cases VOPBA and MS/MS were used to identify candidate binding proteins. The assignment of the two proteins as dengue virus receptors came after functional studies using antibodies directed against the respective proteins to inhibit dengue virus internalization. In the case of the 37/67kDa high affinity laminin receptor protein inhibition was additionally observed in the presence of a natural ligand for this receptor (laminin) and down regulation of the protein was seen in response to infection. In each case ALL serotypes were functionally examined for inhibition effects (although this is not presented in the GRP78/Bip manuscript) and, as stated, the effects were serotype specific.
Additionally the statement that “(Discussion, Page 8, lines 6 to 8):
“ Contrary to earlier suggestions that LAMR1 is a DENV-1 specific receptor protein [14, 16], in our hands, DENV-1, DENV-2 and DENV-3 were all shown to interact with the same molecule LAMR1 although DENV-4 did not”
is also wrong as the authors have confused the ability of the various serotypes to interact (bind) with the 37/67kDa high affinity laminin receptor protein (their study) and the ability of the various serotypes to use the protein as a receptor (our studies).
Moreover the assumption that the HepG2 and PS Clone D are in some way functionally equivalent, and that what is found in one cell line must be correct for others is somewhat simplistic. The simple fact that DC-SIGN has been shown to be a functional receptor for dendritic cells, HSP 70 and 90 for U937 cells (Journal of Virology Apr 2005, 4557-4567) while our group has identified other binding/receptor proteins in other cell types would suggest that the interaction between specific dengue viruses and specific cell types is likely to be highly complex. Lastly, given that the Cardosa study identifies the same protein as a dengue virus binding protein that we have characterized as a dengue virus receptor protein, it is unfortunate that the authors did not seek to keep the nomenclature of this protein the same to avoid future confusion.
Competing interests
None declared