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Referee comments: Referee 2

Posted by PLOS_ONE_Group on 03 Mar 2008 at 11:59 GMT

Referee 2's review:


This is an interesting, but complicated manuscript that add to the ongoing saga of MuHV-4 entry. It tends, however, to take too much for granted that the reader is an aficionado and the basic premises that the authors take for granted could be more clearly explained for the novice.

Specific points:

1. Page 3, second paragraph. For those not intimately acquainted with the MuHV-4 literature this paragraph is very arcane and rather obscure. The authors' model for the role of gp150 should be clearly and simply spelled out as it is critical to understanding the theses of the current manuscript. The analogy with EBV gp350 is interesting and can be extended not only to the B cell transfer of virus but also to observations that antibodies to gp350 can enhance infection of epithelial cells.

2. Figure 1. The graphics are currently of poor quality and it is not always possible to determine which line is which.

3. Page 4, last line. Displaced from what? This becomes clearer later on, but the reader may stay too confused to continue on to find out.

4. Figure 2. It would be better to include the "control" on each histogram as is the norm. It is not possible to tell if gB-N-Fc is binding or not - by eye it looks as though, contrary to the text on page 6, it is not. It is also customary to label both x and y axes.

5. Figure 3B. What is the band just above the 48 kDa marker that is precipitated by heparin-agarose (it seems to blot with antibody to gB in Figure 3C) and why is gp70 so much more prominent in a gL-null virus?

6. Page 8 second paragraph, line 1. What is meant by a "real" interaction? The antibody blocking experiments certainly support the conclusion that gH/gL binds specifically to BHK cells, but they do not directly address the question of whether or not this is binding via GAG.

7. Figure 5 C. How did the second antibody distinguish the blocking antibodies from the anti-gN antibody?

8. Figure 6D. The label on the y axis is difficult to fathom.

9. Figure 7. M7- is presumably the same as gp150-? In these experiments were equal amounts of wild type and gp50- virus used? How should they be compared?

10. Page 13, first paragraph. The "displacement" of gp150 is a very seductive hypothesis, but it really needs to be emphasized that it is just a hypothesis and one possible interpretation of data. There are no definitive experimental data that unequivocally support it as far as this reviewer can tell.

11. Page 16. What are NMuMG cells?

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N.B. These are the comments made by the referee when reviewing an earlier version of this paper. Prior to publication the manuscript has been revised in light of these comments and to address other editorial requirements.