they have found that cleavage also occurs at arginine 
231, which is conserved in all rotavirus strains ana- 
lyzed so far. This may be the site in VP4 that is most 
susceptible to trypsin cleavage. 
In addition, they have shown that digestion of the 
virus with proteolytic enzymes other than trypsin — 
enzymes that generate single cleavages at positions 
24 1 or 245 in VP4 — does not activate viral infectiv- 
ity. After these treatments, however, the virion infec- 
tivity can still be activated by trypsin. The results 
suggest that the hitherto unidentified cleavage site 
at arginine 231 might play a key role in the activa- 
tion of the virus infectivity. Dr. Arias and his col- 
leagues are currently interested in identifying the 
cleavage (s) directly responsible for the enhance- 
ment of viral infectivity and in elucidating the mech- 
anism through which the cleaved VP4 protein medi- 
ates penetration of the virion into the cell. 
Immune Response to Rotavirus Infection 
So far six different serotypes of human rotaviruses 
have been identified, four of which appear to ac- 
count for the great majority of isolates worldwide. 
Dr. Arias and his co-workers have been investigating 
the relationship between the serotype of the infect- 
ing rotavirus and the specificity of the immune re- 
sponse in infected children. In apparently primary 
infections, they have shown that rotaviruses are able 
to induce a neutralizing immune response of a het- 
erotypic nature — i.e., directed to more than one 
serotype — and that this antibody response is elic- 
ited preferentially by viruses of serotypes 2,3, and 
4. The group's current interest is to determine the 
molecular basis of this heterotypic cross-reactive 
immune response, which appears to be an intrinsic 
property of certain rotaviruses. An understanding of 
this immune response could be very helpful in the 
design of vaccines that would protect against a vari- 
ety of rotavirus serotypes. 
Dr. Arias is Investigador Titular B, Department 
of Molecular Biology, at the Biotechnology Insti- 
tute, National Autonomous University of Mexico, 
Cuernavaca. 
Articles 
Lopez, S., and Arias, C.F. 1992. Simian rotavirus 
SAl 1 strains [letter to the editor]./ Wro/ 66:1832. 
Lopez, S., Lopez, I., Romero, P., Mendez, E., So- 
beron, X., and Arias, C.F. 1992. Rotavirus YM 
gene 4: analysis of its deduced amino acid se- 
quence and prediction of the secondary structure 
of the VP4 protein. / Wro/ 65:3738-3745. 
MOLECULAR GENETICS OF CELL SIGNALING IN MAMMALS 
Alan Bernstein, Ph.D., International Research Scholar 
Cells of multicellular organisms need mecha- 
nisms for the transmission and reception of extra- 
cellular signals and for transducing them across the 
plasma membrane to activate intracellular signaling 
pathways that lead to an appropriate proliferative or 
developmental response. The hematopoietic system 
provides a particularly good example of the critical 
role these signaling processes play in regulating the 
orderly production of blood cells. All the cells in the 
blood and in lymphoid organs arise as a result of the 
ongoing proliferative and developmental divisions 
of a hierarchy of pluripotent stem cells that reside in 
the adult bone marrow. Molecular analysis of the 
diseases that result in either under- or overproduc- 
tion of mature blood cells has demonstrated the 
tight controls that govern stem cell function and has 
helped in the dissection of the molecular pathways 
that regulate these cells. 
Control of Hematopoiesis 
Dr. Bernstein's laboratory is attempting to under- 
stand the molecular and cellular basis of normal 
blood cell production by identifying cellular genes 
that play critical roles in this process. Several experi- 
mental approaches are being taken by the group to 
understand this complex system. They are analyzing 
the genes and their protein products that are impor- 
tant to the evolution of the multistage erythroleuke- 
mias induced by various strains of Friend leukemia 
virus. The molecular analysis of existing mouse de- 
velopmental mutations that affect normal hema- 
topoiesis provides a second approach to the identi- 
fication of genes that are critical to cellular 
interactions in the blood-forming system. And fi- 
nally, the introduction of either loss- or gain-of- 
function mutations into the mouse germline of 
genes normally expressed in hematopoietic cells 
500 
