oncogenes are frequently activated by the nearby 
integration of viral DNA sequences into the host 
chromosome in this model system. The implicated 
cellular oncogenes are being cloned and character- 
ized in an attempt to define the molecular basis of 
hepatocyte growth control. 
The laboratory of Investigator Michael M.-C. Lai, 
M.D., Ph.D. (University of Southern California) 
has been studying the molecular biology and the 
disease-inducing mechanisms of two classes of hu- 
man and animal infectious agents, coronaviruses 
and hepatitis delta viruses, both of which contain 
RNA as their genetic materials. These viruses cause 
common colds, hepatitis, and a variety of gastroin- 
testinal and respiratory diseases; they also serve as a 
possible model for multiple sclerosis. This group 
has examined how these viruses grow and make 
their RNAs, and how their genes work to cause dis- 
eases. A unique mechanism of making viral RNA has 
been found, as well as a mechanism of genetic ex- 
change called RNA recombination, which is an im- 
portant tool in virus evolution. Progress also has 
been made in describing the pathway by which virus 
infects cells. This new knowledge is applicable to a 
general understanding of the cause and therapy of 
viral diseases. 
Assistant Investigator Karla A. Kirkegaard, Ph.D. 
(University of Colorado) and her colleagues have 
found that the inhibition of poliovirus replication 
by brefeldin A, an inhibitor of protein secretion, and 
the inhibition of protein secretion by poliovirus in- 
fection both point to the normal protein secretion 
apparatus as the donor of the membranous vesicles 
associated with poliovirus replication complexes. A 
quantitative assay for RNA recombination frequency 
has shown that RNA recombination continues 
throughout the course of poliovirus infection, unaf- 
fected by these major intracellular rearrangements. 
In other work they observed that the ability to initi- 
ate the replicative cycle of L A, a double-stranded 
RNA virus of Saccharomyces cerevisiae, with RNA 
synthesized in vitro from cloned cDNA should lead 
to the development of RNA viral genetics in that 
organism. 
The research in the laboratory of Investigator Rob- 
ert A. Lamb, Ph.D., Sc.D. (Northwestern University) 
concerns the molecular structure and mechanism of 
replication of two enveloped viruses, influenza 
virus and the paramyxovirus SV5 (simian virus 5). 
The imponant diseases in humans and animals 
caused by influenza virus have serious socioeco- 
nomic consequences, because influenza continues 
to occur in regular epidemics, and an occasional 
pandemic, and is a leading cause of morbidity and 
mortality. Among the paramyxoviruses are mumps, 
measles, canine distemper, Newcastle disease of 
chickens, and rinderpest of cattle, as well as SV5, 
the prototype used by Dr. Lamb. Research has fo- 
cused on the structure, function, and mechanism of 
intracellular transport of integral membrane pro- 
teins of the viral envelope and the replication strat- 
egy of the viral RNA genome. In particular, emphasis 
has been placed on understanding the ion channel 
activity of the influenza virus M2 protein, a novel 
activity for a viral protein and believed to be essen- 
tial for uncoating the virus in cells. This viral ion 
channel activity is blocked by the antiviral drug 
amantadine hydrochloride, and Dr. Lamb's work 
provides a molecular explanation for the drug's 
effect. 
Many disease-causing microorganisms are able to 
enter and grow inside human cells. Two such bacte- 
ria are being investigated by Assistant Investigator 
Ralph R. Isberg, Ph.D. (Tufts University) and his col- 
leagues in order to determine how intracellular 
entry and growth occur. One microorganism that 
causes gastrointestinal disease. Yersinia pseudo- 
tuberculosis, was found to enter host cells by bind- 
ing members of the integrin receptor family present 
on a wide variety of host cells. Uptake of the organ- 
ism appears to occur by parasitizing the human 
cell's normal pathway for internalization of macro- 
molecules. Study of the intracellular growth of Le- 
gionella pneumophila, the causative agent of Le- 
gionnaire's disease, found a small region of the 
bacterial chromosome that contains a gene permit- 
ting the organism to enter into the rough endoplas- 
mic reticulum of host phagocytic cells. 
The laboratory of Assistant Investigator Richard H. 
Gomer, Ph.D. (Rice University) is investigating pos- 
sible mechanisms of cell differentiation and the 
ways in which cells sense the number of a given cell 
type that are in an organism. Such mechanisms may 
play an important role in growth, wound healing, 
tissue regeneration, and the control of cell prolifera- 
tion. Using the simple organism Dictyostelium, this 
group employs molecular biologic techniques to 
search for genes involved in the determination of 
which one of its three possible types a Dictyoste- 
lium cell will become. Related studies concern a 
protein that the cells secrete and simultaneously 
sense, allowing them to determine whether they are 
near many or few other cells. 
The laboratory of Associate Investigator Gary K. 
Schoolnik, M.D. (Stanford University) continues to 
study the ecology and pathogenesis of bacteria im- 
portant in human disease. Of special importance 
have been their studies of enteropathogenic Esche- 
CELL BIOLOGY AND REGULATION 1 5 
