Biology Reference
In-Depth Information
conditions, such as those following ultracentrifugation. The S1 subunit
of JHMV is particularly removable, which takes place as a naturally
occurring event.
51,52
This characteristic is thought to be responsible for a
receptor-independent fusion mechanism. The S2 subunit, from which
S1 is removed in a receptor-unmediated fashion, could undergo confor-
mational changes and is fusogenically activated in a way similar to that
found when S1 binds to its receptor and becomes detached from S2.
49
A critical condition for the receptor-independent fusion/infection is that
this activation process of the S protein should be carried out in close
proximity of the target cell membrane. Most recently, this hypothesis was
strengthened by the infection of spinoculation; spinning the inoculated
viruses together with the target receptor-negative cells resulted in the
viruses being attached on the cell surface.
52
The receptor-independent
JHMV infection was suggested to result in its high neurovirulence in
mice.
53
Although it is not so remarkable, some strains of MHV other
than JHMV retain the ability of receptor-independent infection.
54
Concluding Remarks
Although different types of protein are used as receptors for MHV or
SARS-CoV, the cell entry mechanism of these viruses looks very similar
to that first postulated as an entry mechanism for the influenza virus and
HIV. However, the fusogenic activation of the SARS-CoV S protein by
the cell-derived protease under low pH environment is a quite unique
phenomenon. MHV-2 could share this feature and provide an excellent
model for understanding the SARS-CoV entry mechanism. Detailed
molecular studies on the S protein and receptor interactions, as well as
the subsequent cell entry mechanism, will facilitate the development of
anti-SARS-CoV reagents.
Acknowledgments
I greatly appreciate Shutoku Matsuyama for his valuable and stimu-
lating discussions and for illustrations used in this review. I also thank
Keiko Nakagaki, Miyuki Kawase as well as Shigeru Morikawa and his
group members for their continuous discussions and encouragement.
This work is financially supported by grants from the Ministry of
Education, Culture, Sports, Science and Technology (16017308),
