Recombinant Poliovirus Takes China By Storm
A recombinant poliovirus spread 2,200 km from the point of origin
within 2.5 years. Evolutionary and epidemiologic analyses suggest that
the recombinant derives from coinfection in 1991 of one individual with
wild type 1 poliovirus and the Sabin type 1 oral poliovirus vaccine
strain, says first author Hong-Mei Liu, of the U.S. Centers for Disease
Control and Prevention and the National Vaccine and Serum Institute,
Beijing. All recombinants "had a homologous 367-nucleotide block of
sequences, spanning the VP1/2A junction, that was derived from the Sabin
type 1 OPV strain (LSc 2ab)," the authors write. The overall
synonymous substitution rate per synonymous site per year for the
complete VP1 and 2A genetic interval was (3.73 ± 0.52) X 10-2.
"We have found many other natural poliovirus recombinants in
China and other countries, and we would like to learn more about the
frequency, mechanisms, and biological significance of these
recombination events," says Liu.
(H.-M. Liu, D.-P. Zheng, L.-B. Zhang, M. Steven
Oberste, M. A. Pallansch, and O. M. Kew. 2000. Molecular evolution of a
type 1 wild-vaccine poliovirus recombinant during widespread circulation
in China. J. Virol. 74:11153-11161.) Abstract |
Antibiotic Suppresses Surgically Induced Inflammation Absent
Kwok-Yung Yuen of the University of Hong Kong Queen Mary Hospital and
colleagues have shown that clarithromycin, a macrolide antibiotic,
markedly reduced inflammation induced by surgical trauma. In this study,
54 mastectomy patients were randomly divided into two groups, one of
which received 500 mg of clarithromycin from the day before to three
days after mastectomy.
Treatment was associated with attenuation of febrile response,
tachycardia, tachypnea, and an increase in monocyte counts (P
<0.0001, <0.01, <0.05, and <0.01, respectively), and with a
significant reduction in postoperative pain and increased range of
"This is not unexpected because the chemical structure of
macrolides is quite similar to cyclosporin, which is used to prevent
rejection in transplantation," says Yuen. "However, macrolides
do not have the side effects associated with immunosuppression."
Yuen plans further research into antibiotic immunomodulation under both
infectious and noninfectious conditions.
(L. W. C. Chow, K.-Y. Yuen, P. C. Y. Woo, and W. I.
Wei. 2000. Clarythromycin attenuates mastectomy-induced acute
inflammatory response. Clin. Diagn. Lab. Immunol. 7:925-931.) Abstract |
Sensitive Genetic Screen for Protease Activity
Site-specific proteases play a key role in signal transduction,
apoptosis, and many other biological processes. The human
immunodeficiency virus (HIV) protease is essential for infectivity, but
HIV's rapid evolution limits efficiency of protease inhibitors.
Daniel Ladant of the Institut Pasteur, Paris, and colleagues have
developed a genetic screen that makes functional characterization of
proteases easy. They engineer into the middle of the Bordetella
pertussis adenylate cyclase (AC) polypeptide a sequence
corresponding to a specific cleavage site of the HIV protease. Expressed
in AC-deficient Escherichia coli, it restores the normal
phenotype. Adding HIV protease into the cells inactivates the AC. HIV
protease inhibitors such as saquinavir can then restore the normal
"We further showed that HIV protease variants resistant to
particular inhibitors can easily be distinguished from the wild-type
protease," says Ladant. "Given its exquisite sensitivity, this
screening system could be applied more generally, either to screen
libraries for proteases that could cleave a precise peptide sequence, or
conversely to determine the target site of a given protease," says
(N. Dautin, G. Karimova, A. Ullmann, and D. Ladant.
2000. A sensitive genetic screen for protease activity based on a cyclic
AMP signaling cascade in Escherichia coli. J. Bacteriol.
182:7060-7066.) Abstract |
Antiretrovirals Suppress Replication of Pig Retrovirus In Vitro
Pig organs are physiologically suitable for use as human transplants.
However, they have been found to contain porcine endogenous retroviruses
(PERV), which have been shown to infect human cells in vitro, raising
the possibility of transmission.
Ed Otto of Genetic Therapy, Inc., Gaithersburg, Md., and colleagues
have shown in vitro that "AZT is a potent inhibitor of PERV
replication in 293 cells, with a 50% inhibitory concentration (IC50)
of approximately 0.25 m M. DdI also inhibited PERV, with an IC50
of approximately 1 m M," according to this report. "These
concentrations are similar to IC50s reported in in vitro
studies of human immunodeficiency virus type 1 . . . 3TC, d4T, and
indinavir were not effective inhibitors of PERV replication."
"These results demonstrate that PERV replication can be
controlled using standard antiretroviral therapies but that, like MLV,
the virus is inherently resistant to some commonly used therapies,"
the authors conclude.
(S. K. Powell, M. E. Gates, G. Langford, M.-L. Gu, C.
Lockey, Z. Long, and E. Otto. 2000. Antiretroviral agents inhibit
infection of human cells by porcine endogenous retroviruses. Antimicrob.
Agents Chemother. 44:3432-3433.) Abstract |
Novel Pathway Converts Human Fibrosarcoma to Aggressive Phenotype
Recent in vivo studies by Eric Stanbridge of the University of
California, Irvine, and others showed that deleting an endogenous mutant
ras allele from the HT1080 human fibrosarcoma cell line converted
the tumorigenic phenotype from aggressive to weak.
Stanbridge and coworkers now examine multiple signaling pathways,
showing that when downregulated, none affect the aggressive tumorigenic
phenotype of HT1080 cells. "Conversely, overexpression of activated
MEK in the cells that lack a mutant ras allele converts them from
weak to aggressively tumorigenic," says Stanbridge.
"Comparison of the various dominant-negative and constitutively
active transfectants indicates that overexpression of activated MEK is
critical and activates target(s) that convert(s) the cells to an
Stanbridge seeks to identify these targets in order to determine the
ultimate trigger for aggressive tumor growth. That, he says, "may
provide further pharmacologic opportunities for therapeutic
(S. Gupta, R. Plattner, C. J. Der and E. J. Stanbridge.
2000. Dissection of ras-dependent signaling pathways controlling
aggressive tumor growth of human fibrosarcoma cells: evidence for a
potential novel pathway. Mol. Cell Biol. 20:9294-9306.) Abstract |
Macrophages Infected with C. trachomatis Induce T Cell
Apoptosis: Mechanism May Cause Persistent Arthritis
Recent research has shown that live, metabolically active Chlamydia
trachomatis (CT) in the inflamed joint are responsible for the
persistence of CT-induced arthritis, an untreatable condition.
Michael C. Jendro and colleagues of the Medical School Hannover,
Germany, have shown that CT-infected macrophages can induce T cell
apoptosis. That, says Jendro, "may explain how persistently
infected macrophages escape T cell surveillance and why the Chlamydia-specific
T cell response is diminished during persistent chlamydial infection. By
modulating this mechanism with anti-apoptotic antibodies or reagents we
can possibly prevent T cell apoptosis. This might lead to a better anti-chlamydial
T cell response, and hopefully to eradication of these bacteria."
"We are investigating the molecular mechanism by which the
CT-infected macrophages execute T cells; whether CT-induced apoptosis
occurs in vivo, and whether different chlamydial species share this
capability," says Jendro.
(M. C. Jendro, T. Deutsch, B. Korber, L. Kohler, J. G.
Kuipers, B. Krausse-Opatz, J. Westermann, E. Raum, and H. Zeidler. 2000.
Infection of human monocyte-derived macrophages with Chlamydia
trachomatis induces apoptosis of T cells: a potential mechanism for
persistent infection. Infect. Immun. 68:6704-6711.) Abstract |