Previous Article | Next Article 
Antimicrobial Agents and Chemotherapy, November 2000, p. 3150-3154, Vol. 44, No. 11
CEA, Service de Neurovirologie, DSV/DRM,
CRSSA, EPHE, Institut Paris-Sud sur les Cytokines, Fontenay aux
Roses,1 Université Denis Diderot-Paris
VII, Laboratoire de Pharmacochimie Moléculaire,
Paris,2 and SPI-BIO, Massy,3
France
Received 19 November 1999/Returned for modification 3 March
2000/Accepted 28 July 2000
We assessed the anti-human immunodeficiency virus (anti-HIV)
activity in vitro of new platelet-activating factor (PAF) receptor antagonists, as PAF and viral replication are thought to be involved in
HIV neuropathogenesis. We found that PMS-601 inhibited proinflammatory cytokine synthesis and HIV replication in macrophages and
potentiated the antiretroviral activity of zidovudine. These results
suggest that PMS-601 is of potential value as an adjuvant treatment for HIV infection.
Human immunodeficiency virus (HIV)
type 1 (HIV-1)- associated dementia complex (ADC) is a frequent
complication of progressive HIV infection (16, 21). The
neuropathogenesis of HIV infection involves (i) the entry of the virus
into the central nervous system (CNS), (ii) the production of viral and
cellular components that mediate inflammation and neurotoxicity, and
(iii) neuronal dysfunction and death. Gendelman et al. (14)
recently provided evidence that metabolic encephalopathy is fueled by
HIV replication. Infection of the CNS with HIV typically involves
selective replication in mononuclear phagocytes and microglial cells,
cell activation, and chronic inflammation (15, 32), leading
to high levels of proinflammatory compounds (11, 17, 19, 29)
such as tumor necrosis factor alpha (TNF- Monocytes were isolated from peripheral blood mononuclear cells by
countercurrent centrifugal elutriation (9). Monocytes, macrophages that had been differentiated for 7 days, and
promonocytic U1 cells (10) were cultured in medium A, which
consisted of RPMI 1640 cell culture medium (Roche Products, Mannheim,
Germany) supplemented with 10% heat-inactivated (56°C for 30 min) fetal calf serum (Roche Products), 2 mM L-glutamine
(Roche Products), and 1% triantibiotic mixture (penicillin,
streptomycin, neomycin; Life Technologies, Grand Island, N.Y.). The
cell culture medium was endotoxin-free, as shown by the
Limulus amoebocyte lysate test (Sigma Chemical Co, St.
Louis, Mo.). The chemically synthesized molecule PMS-601 [1,4-di-(3',4',5'-trimethoxybenzoyl)-2-(N,N-diethylaminocarbonyloxymethyl)-piperazine] inhibits platelet aggregation, with a 50% effective dose
(ED50) of 8 µM (28). The involvement of PAF in
the lipopolysaccharide (LPS)-induced synthesis of proinflammatory
cytokines (18, 31) led us to study the effects of PMS-601 on
the secretion of these molecules. TNF-
0066-4804/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.
PMS-601, a New Platelet-Activating Factor Receptor Antagonist
That Inhibits Human Immunodeficiency Virus Replication and
Potentiates Zidovudine Activity in Macrophages
ABSTRACT
Top
Abstract
Text
References
TEXT
Top
Abstract
Text
References
), 
-chemokines, and
platelet-activating factor (PAF) (5, 13, 19, 27). The
correlation between PAF levels in the cerebrospinal fluid and the
severity of clinical dementia suggests a possible role for PAF in
immune activation and neuropathological mechanisms (8, 22).
Several studies have demonstrated a major slowing of HIV-1 disease
progression in patients treated with highly active antiretroviral
therapy (HAART) (3, 23). However, this treatment may have
less of an impact on ADC than on other AIDS-defining illnesses
due to the poor penetration of the drugs into the CNS (7).
As PAF and virus replication are thought to be involved in HIV
neuropathogenesis, we assessed the anti-HIV activities of piperazine
derivatives that function as antagonists of the PAF receptor
(28). We describe herein the effects of the most promising
molecule, PMS-601, on proinflammatory cytokine synthesis, HIV
replication, and the antiretroviral effects of zidovudine (AZT) in
monocytes/macrophages.
and -chemokine levels in
cell culture supernatants of monocytes stimulated with LPS for 2 h
were measured by using an enzyme-linked immunosorbent assay specific
for detection of each cytokine (R&D [Oxon, United Kingdom] for
chemokines; Immunotech [Luminy, France] for TNF-). Under these
experimental conditions, the increase in the levels of TNF-,
MIP-1, MIP-1, and RANTES secreted by induction with
100 ng of LPS per ml was significantly decreased by PMS-601 (27, 29, 17, and 42% inhibition, respectively) (Fig.
1). These anti-inflammatory properties
correlated with the anti-PAF activity of PMS-601. The antiretroviral
activity of PMS-601 was evaluated with macrophages that had
been differentiated for 7 days and that had been infected with
reference macrophage-tropic strain HIV-1/Ba-L (12,
28) or with a primary macrophage-tropic isolate,
HIV-1-DAS (2) or HIV-1-THI (6). Viral replication was assessed by quantifying the reverse transcriptase (RT) activity in
the cell culture supernatant (RetroSys; Innovagen, Lund, Sweden) and
the antiretroviral effects of PMS-601 by determining the cumulative RT
activity, the percentage of the control RT activity, and the ED50, ED70, and ED90. As shown
previously (6), the reference macrophage-tropic
strain HIV-1/Ba-L and primary macrophage-tropic isolates
HIV-1-DAS and HIV-1-THI replicated efficiently in macrophages, with optimal replication occurring between days 15 and 25 postinfection. Against these HIV-infected macrophages, PMS-601
exhibited similar levels of dose-dependent antiretroviral activity
(Fig. 2A; data not shown for strains
HIV-1-DAS and HIV-1-THI) for the three viruses tested. The mean
ED50, ED70, and ED90 were 10, 30, and 100 µM, respectively. This antiviral activity was not associated
with a decrease in cell viability even after 30 days of treatment with 1 mM PMS-601 (Fig. 3A) (selectivity index
[SI], >100). The antiretroviral efficiency of PMS-601 in
macrophages was confirmed by the inhibition of viral
replication (65% inhibition) when cells were exposed to PMS-601 for
24 h (Fig. 2B). HIV replication in macrophages is partly
dependent on TNF-. The effects of PMS-601 on TNF--dependent HIV
production in chronically HIV-infected promonocytic U1 cells were
investigated. HIV production was greatly decreased by 100 µM PMS-601
and by 0.5 µM indinavir (Fig. 2C) (for PMS-601, a 70% decrease; for
indinavir, an 81% decrease); this effect was not associated with
a decrease in cell growth (Fig. 3B). PMS-601 could be used as adjuvant
therapy with antiretroviral molecules, particularly nucleoside RT
inhibitors (NRTIs), due to its effects on the late steps in the
biological cycle of HIV. We therefore assessed the effects of PMS-601
on the antiretroviral efficiency of AZT by treating macrophages
simultaneously with PMS-601 and AZT. In these cells, AZT inhibited
HIV-1/Ba-L replication, with an ED50 of 15 nM (Fig.
4), and PMS-601 increased the
antiretroviral efficiency of AZT. These effects were additive, as shown
by (i) a combination index (CI) of 1, (ii) the decrease in viral
replication by 73% by use of an ineffective dose of AZT (1 nM) in
association with a dose of PMS-601 that inhibited 46% of viral
replication when used alone, and (iii) the complete abolition of viral
replication by 10 µM PMS-601 (46% inhibition when used alone) when
it was used in association with 10 nM AZT (48% inhibition) (Fig. 4). Another PAF antagonist previously evaluated in our laboratory, RP55778,
showed antagonism with AZT (4). RP55778 also decreased cell
viability and had no antiviral activity in lymphocytes, whereas PMS-601
decreased the levels of HIV-1/Ba-L and HIV-1-LAI replication (ED50, 5 µM) but had no effect on cell growth when it was
used at a concentration of less than 125 µM (Fig. 3C) (50% cytotoxic concentration, 280 ± 90 µM; SI, 
50).
View larger version (20K):
[in a new window]
FIG. 1.
Effect of PMS-601 on the production of TNF- and
chemokines in LPS-stimulated monocytes. Monocytes were simultaneously
stimulated for 2 h with the optimal dose (100 ng/ml) of bacterial
LPS (Escherichia coli serotype O111:B4; Sigma) and treated
with 100 µM PMS-601. PMS-601 was dissolved in dimethyl sulfoxide
(Prolabo, Fontenay/Bois, France), and the corresponding dose of
dimethyl sulfoxide without PMS-601 was used as a control. This dose of
dimethyl sulfoxide had no significant effect on the synthesis of
proinflammatory cytokines. These experiments were performed in
triplicate at least twice. Data are expressed as a percentage of the
control and were analyzed by Student's unpaired t test
(Statview, version 4.02, microcomputer software; Abacus Concept Inc.,
Berkeley, Calif.). 
, untreated control;
, monocytes
treated with 100 µM PMS-601.
View larger version (26K):
[in a new window]
FIG. 2.
Effects of long-term treatment (A) and 24-h treatment
(B) with PMS-601 on HIV-1/Ba-L replication in macrophages. A
total of 105 cells were infected with 1,000 50% tissue
culture infective doses on day 0, and viral replication was determined
throughout the culture period by quantifying the RT activity in the
cell culture supernatant. Data are expressed as the mean ± standard deviation RT activity for three independent culture wells. (C)
Effects of PMS-601 on HIV-1 production in chronically HIV-infected
promonocytic cells. U1 cells were simultaneously stimulated with
TNF- (10 ng/ml) and treated with 100 µM PMS-601, which was
noncytostatic. HIV particle production was measured after 48 h of
incubation by quantifying the RT activity in the cell culture
supernatant. Data are expressed as the mean ± standard deviation
percent inhibition for four independent culture wells. These
experiments were reproduced with cells from at least three independent
healthy donors. DMSO, dimethyl sulfoxide.
View larger version (38K):
[in a new window]
FIG. 3.
Effects of PMS-601 on primary macrophage (A),
promonocytic U1 cell (B), and peripheral blood lymphocyte (C)
viability. Cells were treated throughout the culture with a range of
PMS-601 doses and were counted either by trypan blue staining (for
healthy lymphocytes and promonocytic U1 cells) or by neutral red
staining, using a standard curve (for healthy macrophages).
Data are representative of experiments performed with cells from three
independent healthy blood donors.
View larger version (60K):
[in a new window]
FIG. 4.
Effects of PMS-601 on the antiretroviral efficacy of AZT
in macrophages. Cells were treated with various associations of
PMS-601 and AZT and were infected with 1,000 50% tissue culture
infective doses/105 cells infected with reference strain
HIV-1/Ba-L. Results are expressed as the mean ± standard
deviation percent inhibition for three independent culture wells on the
basis of the cumulative RT activity. Data were analyzed by Student's
unpaired t test (Statview, version 4.02, microcomputer
software; Abacus Concept Inc.). These experiments were reproduced with
cells from three independent healthy donors.
Our results show that PMS-601, a PAF receptor antagonist, combines
significant anti-inflammatory and broad antiretroviral properties.
Nevertheless, the lack of correlation between the anti-PAF and
antiretroviral activities of the members of this family of piperazine
derivatives (28) suggests that the antiretroviral activity
of PMS-601 was not solely due to its anti-PAF and anti-inflammatory properties. PMS-601 probably also has other biological effects. The
inhibition of viral replication observed for the 24-h treatment of
macrophages and comparison of the properties of PMS-601 and RP55778 support this idea. First, the results of the 24-h treatment experiment strongly suggest that PMS-601 interacts with an early stage
of the HIV biological cycle. However, its precise mode of action is not
yet clear: no significant modulation of RT activity was detected, and
specific interaction with HIV-1 coreceptors is unlikely because PMS-601
inhibited similarly the replication of viral strains that differed in
their binding to HIV coreceptors (1). Second, RP55778,
another PAF receptor antagonist, has been shown to have anti-HIV-1 and
anti-inflammatory effects in vitro against cells of the
macrophage lineage (20, 30). Like PMS-601, RP55778
decreased the levels of TNF- production and the release of HIV
particles from monocytes/macrophages. However, RP55778
had no antiviral activity in lymphocytes and reduced the antiretroviral
efficiency of NRTIs, particularly that of AZT (CI, 10)
(4). The potentiation of the effects of AZT is a key
property in favor of the use of PMS-601 as an adjuvant therapy with
NRTIs. In some tissues, such as those of the CNS, HIV replication is not completely abolished by HAART. Instead, it is maintained by the
inflammatory environment that exists in parallel with monocyte recruitment (24, 25). Due to its various biological
properties and its lipophilicity, PMS-601 is an excellent candidate
molecule for decreasing HIV replication, leukocyte recruitment, and
invasive tissue inflammation.
Our results, obtained in vitro, suggest that the piperazine derivative PMS-601 may effectively decrease the neuropathological symptoms associated with HIV. Recent data obtained from studies with HIV-infected patients treated with lexipafant, another PAF receptor antagonist, provide further evidence that this type of molecule may be valuable for the future treatment of certain symptoms associated with HIV infection (26).
| |
ACKNOWLEDGMENTS |
|---|
We thank the Centre de Transfusion Sanguine des Armées (Clamart, France), the Service de Cytaphérèse de l'Hôpital Saint-Louis (Paris, France), and the Maternité Sainte-Félicité (Paris, France) for providing buffy coats and umbilical cord blood. U1 cells were obtained through the AIDS Research and Reference Reagent Program, Division of AIDS, National Institute of Allergy and Infectious Diseases, National Institutes of Health; U1/HIV-1 was obtained from Thomas Folks.
This work was supported by the Agence Nationale de Recherches sur le SIDA (Paris, France), the Fondation pour la Recherche Médicale (Sidaction, Paris, France), the Institut de Formation Supérieure Biomédicale (Villejuif, France), the Université Denis Diderot-Paris VII, the Commissariat à l'Energie Atomique (Paris, France), the Association pour la Recherche en Neurovirologie (Griselles, France), the Association "Claude Bernard" (Paris, France), and the Association "Naturalia & Biologia" (Paris, France).
| |
FOOTNOTES |
|---|
* Corresponding author. Mailing address: Service de Neurovirologie, CEA/DSV/DRM/CRSSA, 60-68, avenue de la Division Leclerc, B.P. 6, 92265 Fontenay aux Roses Cedex, France. Phone: 33 (0)1 46 54 87 69. Fax: 33 (0)1 46 54 77 26. E-mail: clayette{at}dsvidf.cea.fr.
| |
REFERENCES |
|---|
|
Top
Abstract
Text
References
|
|---|
| 1. | Berger, E. A., R. W. Doms, E. M. Fenyo, B. T. Korber, D. R. Littman, J. P. Moore, Q. J. Sattentau, H. Schuitemaker, J. Sodroski, and R. A. Weiss. 1998. A new classification for HIV-1. Nature 391:240[CrossRef][Medline]. |
| 2. | Boussin, F., D. Dormont, Y. Merrouche, H. Fleury, D. Dubeaux, D. Becquet, J. Goasguen, and P. Brunet. 1987. Possible involvement of HIV in neuropsychiatric episode in a patient seronegative for two (or more) years. Lancet ii:571. |
| 3. | Brodt, H. R., B. S. Kamps, P. Gute, B. Knupp, S. Staszewski, and E. B. Helm. 1997. Changing incidence of AIDS-defining illnesses in the era of antiretroviral combination therapy. AIDS 11:1731-1738[CrossRef][Medline]. |
| 4. |
Clayette, P.,
N. Dereuddre-Bosquet,
M. Martin,
P. Fretier, and D. Dormont.
1997.
Effects of RP 55778, a tumor necrosis factor alpha synthesis inhibitor, on antiviral activity of dideoxynucleosides.
Antimicrob. Agents Chemother.
41:875-877 |
| 5. |
Conant, K.,
A. Garzino-Demo,
A. Nath,
J. C. McArthur,
W. Halliday,
C. Power,
R. C. Gallo, and E. O. Major.
1998.
Induction of monocyte chemoattractant protein-1 in HIV-1 Tat-stimulated astrocytes and elevation in AIDS dementia.
Proc. Natl. Acad. Sci. USA
95:3117-3121 |
| 6. | Dereuddre-Bosquet, N., P. Clayette, M. Martin, O. Benveniste, P. Fretier, P. Jaccard, B. Vaslin, A. Lebeaut, and D. Dormont. 1997. Lack of interleukin-10 expression in monocyte-derived macrophages in response to in vitro infection by HIV type 1 isolates. AIDS Res. Hum. Retrovir. 13:961-965[Medline]. |
| 7. | Dore, G. J., P. K. Correll, Y. Li, J. M. Kaldor, D. A. Cooper, and B. J. Brew. 1999. Changes to AIDS dementia complex in the era of highly active antiretroviral therapy. AIDS 13:1249-1253[CrossRef][Medline]. |
| 8. | Dubois, C., E. Bissonnette, and M. Rola-Pleszczynski. 1989. Platelet-activating factor (PAF) enhances tumor necrosis factor production by alveolar macrophages. Prevention by PAF receptor antagonists and lipoxygenase inhibitors. J. Immunol. 143:964-970[Abstract]. |
| 9. | Figdor, C., J. Leemans, W. Bont, and J. Vries. 1983. Theory and practice of centrifugal elutriation (CE): factors influencing the separation of human blood cells. Cell Biophys. 5:105-118[Medline]. |
| 10. | Folks, T. M., J. Justement, A. Kinter, S. Schnittman, J. Orenstein, G. Poli, and A. S. Fauci. 1988. Characterization of a promonocyte clone chronically infected with HIV and inducible by 13-phorbol-12-myristate acetate. J. Immunol. 140:1117-1122[Abstract]. |
| 11. | Gallo, P., K. Frei, C. Rordorf, J. Lazdins, B. Tavolato, and A. Fontana. 1989. Human immunodeficiency virus type 1 (HIV-1) infection of the central nervous system: an evaluation of cytokines in cerebrospinal fluid. J. Neuroimmunol. 23:109-116[CrossRef][Medline]. |
| 12. |
Gartner, S.,
P. Markovits,
D. Markovitz,
M. Kaplan,
R. Gallo, and M. Popovic.
1986.
The role of mononuclear phagocytes in HTLV-III/LAV infection.
Science
233:215-219 |
| 13. |
Gelbard, H. A.,
H. S. Nottet,
S. Swindells,
M. Jett,
K. A. Dzenko,
P. Genis,
R. White,
L. Wang,
Y. B. Choi,
D. Zhang,
S. A. Lipton,
W. W. Tourtellotte,
L. G. Epstein, and H. E. Gendelman.
1994.
Platelet-activating factor: a candidate human immunodeficiency virus type 1-induced neurotoxin.
J. Virol.
68:4628-4635 |
| 14. | Gendelman, H. E., J. Zheng, C. L. Coulter, A. Ghorpade, M. Che, M. Thylin, R. Rubocki, Y. Persidsky, F. Hahn, J. Reinhard, Jr., and S. Swindells. 1998. Suppression of inflammatory neurotoxins by highly active antiretroviral therapy in human immunodeficiency virus-associated dementia. J. Infect. Dis. 178:1000-1007[Medline]. |
| 15. | Glass, J. D., H. Fedor, S. L. Wesselingh, and J. C. McArthur. 1995. Immunocytochemical quantitation of human immunodeficiency virus in the brain: correlations with dementia. Ann. Neurol. 38:755-762[CrossRef][Medline]. |
| 16. | Gray, F., F. Scaravilli, I. Everall, F. Chretien, S. An, D. Boche, H. Adle-Biassette, L. Wingertsmann, M. Durigon, B. Hurtrel, F. Chiodi, J. Bell, and P. Lantos. 1996. Neuropathology of early HIV-1 infection. Brain Pathol. 6:1-15[Medline]. |
| 17. | Heyes, M. P., B. J. Brew, K. Saito, B. J. Quearry, R. W. Price, K. Lee, R. B. Bhalla, M. Der, and S. P. Markey. 1992. Inter-relationships between quinolinic acid, neuroactive kynurenines, neopterin and beta 2-microglobulin in cerebrospinal fluid and serum of HIV-1-infected patients. J. Neuroimmunol. 40:71-80[CrossRef][Medline]. |
| 18. | Im, S. Y., S. J. Han, H. M. Ko, J. H. Choi, S. B. Chun, D. G. Lee, T. Y. Ha, and H. K. Lee. 1997. Involvement of nuclear factor-kappa B in platelet-activating factor-mediated tumor necrosis factor-alpha expression. Eur. J. Immunol. 27:2800-2804[Medline]. |
| 19. | Kelder, W., J. C. McArthur, T. Nance-Sproson, D. McClernon, and D. E. Griffin. 1998. Beta-chemokines MCP-1 and RANTES are selectively increased in cerebrospinal fluid of patients with human immunodeficiency virus-associated dementia. Ann. Neurol. 44:831-835[CrossRef][Medline]. |
| 20. | Le Naour, R., H. Raoul, A. Mabondzo, Y. Henin, A. Bousseau, and D. Dormont. 1994. Treatment of human monocyte-derived macrophages with a TNF-alpha synthesis inhibitor prior to HIV1 infection: consequences on cytokine production and viral replication. Res. Virol. 145:199-207[Medline]. |
| 21. | McArthur, J. C. 1987. Neurologic manifestations of AIDS. Medicine (Baltimore) 66(6):407-437[Medline]. |
| 22. | Miguelez, R., I. Palacios, F. Navarro, S. Gutierrez, O. Sanchez-Pernaute, J. Egido, E. Gonzalez, and G. Herrero-Beaumont. 1996. Anti-inflammatory effect of a PAF receptor antagonist and a new molecule with antiproteinase activity in an experimental model of acute urate crystal arthritis. J. Lipid Mediat. Cell Signal 13:35-49[CrossRef][Medline]. |
| 23. |
Palella, F., Jr.,
K. M. Delaney,
A. C. Moorman,
M. O. Loveless,
J. Fuhrer,
G. A. Satten,
D. J. Aschman, and S. D. Holmberg.
1998.
Declining morbidity and mortality among patients with advanced human immunodeficiency virus infection. HIV Outpatient Study Investigators.
N. Engl. J. Med.
338:853-860 |
| 24. |
Persidsky, Y.,
A. Ghorpade,
J. Rasmussen,
J. Limoges,
X. J. Liu,
M. Stins,
M. Fiala,
D. Way,
K. S. Kim,
M. H. Witte,
M. Weinand,
L. Carhart, and H. E. Gendelman.
1999.
Microglial and astrocyte chemokines regulate monocyte migration through the blood-brain barrier in human immunodeficiency virus-1 encephalitis.
Am. J. Pathol.
155:1599-1611 |
| 25. | Sanders, V. J., C. A. Pittman, M. G. White, G. Wang, C. A. Wiley, and C. L. Achim. 1998. Chemokines and receptors in HIV encephalitis. AIDS 12:1021-1026[CrossRef][Medline]. |
| 26. |
Schifitto, G.,
N. Sacktor,
K. Marder,
M. P. McDermott,
J. C. McArthur,
K. Kieburtz,
S. Small, and L. G. Epstein.
1999.
Randomized trial of the platelet-activating factor antagonist lexipafant in HIV-associated cognitive impairment. Neurological AIDS Research Consortium.
Neurology
53:391-396 |
| 27. |
Schmidtmayerova, H.,
H. S. Nottet,
G. Nuovo,
T. Raabe,
C. R. Flanagan,
L. Dubrovsky,
H. E. Gendelman,
A. Cerami,
M. Bukrinsky, and B. Sherry.
1996.
Human immunodeficiency virus type 1 infection alters chemokine, beta peptide expression in human monocytes: implications for recruitment of leukocytes into brain and lymph nodes.
Proc. Natl. Acad. Sci. USA
93:700-704 |
| 28. | Serradji, N., O. Bensaïd, M. Martin, E. Kan, N. Dereuddre-Bosquet, J. Huet, F. Heymans, A. Lamouri, P. Clayette, C. Z. Dong, D. Dormont, and J.-J. Godfroid. 2000. Structure-activity relationships in platelet-activating factor (PAF). 10. From PAF-antagonism to inhibition of HIV-1 replication. J. Med. Chem. 43:2149-2154[CrossRef][Medline]. |
| 29. | Tyor, W. R., J. D. Glass, J. W. Griffin, P. S. Becker, J. C. McArthur, L. Bezman, and D. E. Griffin. 1992. Cytokine expression in the brain during the acquired immunodeficiency syndrome. Ann. Neurol. 31:349-360[CrossRef][Medline]. |
| 30. |
Weissman, D.,
G. Poli,
A. Bousseau, and A. S. Fauci.
1993.
A platelet-activating factor antagonist, RP 55778, inhibits cytokine-dependent induction of human immunodeficiency virus expression in chronically infected promonocytic cells.
Proc. Natl. Acad. Sci. USA
90:2537-2541 |
| 31. | Yamada, M., A. Tanimoto, G. Ichinowatari, H. Yaginuma, and K. Ohuchi. 1999. Possible participation of intracellular platelet-activating factor in tumor necrosis factor-alpha production by rat peritoneal macrophages. Eur. J. Pharmacol. 374:341-350[CrossRef][Medline]. |
| 32. | Zheng, J., and H. E. Gendelman. 1997. The HIV-1 associated dementia complex: a metabolic encephalopathy fueled by viral replication in mononuclear phagocytes. Curr. Opin. Neurol. 10:319-325[Medline]. |
Antimicrobial Agents and Chemotherapy, November 2000, p. 3150-3154, Vol. 44, No. 11
0066-4804/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.
This article has been cited by other articles:
-
Dioszeghy, V., Benlhassan-Chahour, K., Delache, B., Dereuddre-Bosquet, N., Aubenque, C., Gras, G., Le Grand, R., Vaslin, B.
(2006). Changes in Soluble Factor-Mediated CD8+ Cell-Derived Antiviral Activity in Cynomolgus Macaques Infected with Simian Immunodeficiency Virus SIVmac251: Relationship to Biological Markers of Progression. J. Virol.
80: 236-245
[Abstract] [Full Text] -
Pereira, C. F., Paridaen, J. T. M. L., van de Bovenkamp, M., Middel, J., Verhoef, J., Nottet, H. S. L. M.
(2003). APHS can act synergically with clinically available HIV-1 reverse transcriptase and protease inhibitors and is active against several drug-resistant HIV-1 strains in vitro. J Antimicrob Chemother
51: 1181-1189
[Abstract] [Full Text]
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Copyright © 2010 by the American Society for Microbiology. For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»