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Candidate Microbicide PPCM Blocks Human Immunodeficiency Virus Type 1 Infection in Cell and Tissue Cultures and Prevents Genital Herpes in a Murine Model
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| Zeitschriftentitel: | Journal of Virology |
|---|---|
| Personen und Körperschaften: | , , , , , , |
| In: | Journal of Virology, 82, 2008, 13, S. 6576-6584 |
| Format: | E-Article |
| Sprache: | Englisch |
| veröffentlicht: |
American Society for Microbiology
|
| Schlagwörter: |
| author_facet |
Mesquita, Pedro M. M. Wilson, Sarah S. Manlow, Philippe Fischetti, Lucia Keller, Marla J. Herold, Betsy C. Shattock, Robin J. Mesquita, Pedro M. M. Wilson, Sarah S. Manlow, Philippe Fischetti, Lucia Keller, Marla J. Herold, Betsy C. Shattock, Robin J. |
|---|---|
| author |
Mesquita, Pedro M. M. Wilson, Sarah S. Manlow, Philippe Fischetti, Lucia Keller, Marla J. Herold, Betsy C. Shattock, Robin J. |
| spellingShingle |
Mesquita, Pedro M. M. Wilson, Sarah S. Manlow, Philippe Fischetti, Lucia Keller, Marla J. Herold, Betsy C. Shattock, Robin J. Journal of Virology Candidate Microbicide PPCM Blocks Human Immunodeficiency Virus Type 1 Infection in Cell and Tissue Cultures and Prevents Genital Herpes in a Murine Model Virology Insect Science Immunology Microbiology |
| author_sort |
mesquita, pedro m. m. |
| spelling |
Mesquita, Pedro M. M. Wilson, Sarah S. Manlow, Philippe Fischetti, Lucia Keller, Marla J. Herold, Betsy C. Shattock, Robin J. 0022-538X 1098-5514 American Society for Microbiology Virology Insect Science Immunology Microbiology http://dx.doi.org/10.1128/jvi.00335-08 <jats:title>ABSTRACT</jats:title> <jats:p> A structurally novel candidate microbicide, PPCM, which is formed from the reaction of <jats:sc>d,l</jats:sc> -mandelic acid with sulfuric acid, provides activity against human immunodeficiency virus (HIV) and herpes simplex virus (HSV) and is not cytotoxic. The objectives of the current studies were to comprehensively evaluate the activity of PPCM in cell and explant cultures, explore the possibility of combining PPCM with HIV-specific reverse transcriptase inhibitors, and evaluate the efficacy of a formulated gel against genital herpes in a murine model. PPCM inhibited infection by laboratory and clinical R5 and X4 clade B and clade C HIV strains in cell culture. Ectocervical and endocervical tissue explants exposed to HIV-1 <jats:sub>BaL</jats:sub> in the presence of PPCM were protected (50% inhibitory concentrations [IC <jats:sub>50</jats:sub> ] of 3.9 μg/ml for ectocervix and 3.1 μg/ml for endocervix), and transfer of virus to target T cells via migratory cells was significantly impaired (IC <jats:sub>50</jats:sub> of 35.7 μg/ml for ectocervix and 54.6 μg/ml for endocervix). The drug also blocked infection by cell-associated virus. Combinations of PPCM with UC-781 or PMPA in vitro exhibited additive anti-HIV activity. PPCM was incorporated into stable, low-pH gel formulations at concentrations of 0.4% and 4%. Both gels prevented genital herpesvirus infection in mice, even when virus was introduced in human seminal plasma. The abilities of PPCM to inhibit primary HIV isolates, reduce infection by cell-associated virus, and transfer of HIV from migratory to T cells, combined with the complete protection provided by formulated gel against genital herpes, indicate that this drug is an excellent candidate for inclusion in a combination microbicide and would provide protection against both HIV and HSV. </jats:p> Candidate Microbicide PPCM Blocks Human Immunodeficiency Virus Type 1 Infection in Cell and Tissue Cultures and Prevents Genital Herpes in a Murine Model Journal of Virology |
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American Society for Microbiology, 2008 |
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American Society for Microbiology, 2008 |
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| title |
Candidate Microbicide PPCM Blocks Human Immunodeficiency Virus Type 1 Infection in Cell and Tissue Cultures and Prevents Genital Herpes in a Murine Model |
| title_unstemmed |
Candidate Microbicide PPCM Blocks Human Immunodeficiency Virus Type 1 Infection in Cell and Tissue Cultures and Prevents Genital Herpes in a Murine Model |
| title_full |
Candidate Microbicide PPCM Blocks Human Immunodeficiency Virus Type 1 Infection in Cell and Tissue Cultures and Prevents Genital Herpes in a Murine Model |
| title_fullStr |
Candidate Microbicide PPCM Blocks Human Immunodeficiency Virus Type 1 Infection in Cell and Tissue Cultures and Prevents Genital Herpes in a Murine Model |
| title_full_unstemmed |
Candidate Microbicide PPCM Blocks Human Immunodeficiency Virus Type 1 Infection in Cell and Tissue Cultures and Prevents Genital Herpes in a Murine Model |
| title_short |
Candidate Microbicide PPCM Blocks Human Immunodeficiency Virus Type 1 Infection in Cell and Tissue Cultures and Prevents Genital Herpes in a Murine Model |
| title_sort |
candidate microbicide ppcm blocks human immunodeficiency virus type 1 infection in cell and tissue cultures and prevents genital herpes in a murine model |
| topic |
Virology Insect Science Immunology Microbiology |
| url |
http://dx.doi.org/10.1128/jvi.00335-08 |
| publishDate |
2008 |
| physical |
6576-6584 |
| description |
<jats:title>ABSTRACT</jats:title>
<jats:p>
A structurally novel candidate microbicide, PPCM, which is formed from the reaction of
<jats:sc>d,l</jats:sc>
-mandelic acid with sulfuric acid, provides activity against human immunodeficiency virus (HIV) and herpes simplex virus (HSV) and is not cytotoxic. The objectives of the current studies were to comprehensively evaluate the activity of PPCM in cell and explant cultures, explore the possibility of combining PPCM with HIV-specific reverse transcriptase inhibitors, and evaluate the efficacy of a formulated gel against genital herpes in a murine model. PPCM inhibited infection by laboratory and clinical R5 and X4 clade B and clade C HIV strains in cell culture. Ectocervical and endocervical tissue explants exposed to HIV-1
<jats:sub>BaL</jats:sub>
in the presence of PPCM were protected (50% inhibitory concentrations [IC
<jats:sub>50</jats:sub>
] of 3.9 μg/ml for ectocervix and 3.1 μg/ml for endocervix), and transfer of virus to target T cells via migratory cells was significantly impaired (IC
<jats:sub>50</jats:sub>
of 35.7 μg/ml for ectocervix and 54.6 μg/ml for endocervix). The drug also blocked infection by cell-associated virus. Combinations of PPCM with UC-781 or PMPA in vitro exhibited additive anti-HIV activity. PPCM was incorporated into stable, low-pH gel formulations at concentrations of 0.4% and 4%. Both gels prevented genital herpesvirus infection in mice, even when virus was introduced in human seminal plasma. The abilities of PPCM to inhibit primary HIV isolates, reduce infection by cell-associated virus, and transfer of HIV from migratory to T cells, combined with the complete protection provided by formulated gel against genital herpes, indicate that this drug is an excellent candidate for inclusion in a combination microbicide and would provide protection against both HIV and HSV.
</jats:p> |
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| author | Mesquita, Pedro M. M., Wilson, Sarah S., Manlow, Philippe, Fischetti, Lucia, Keller, Marla J., Herold, Betsy C., Shattock, Robin J. |
| author_facet | Mesquita, Pedro M. M., Wilson, Sarah S., Manlow, Philippe, Fischetti, Lucia, Keller, Marla J., Herold, Betsy C., Shattock, Robin J., Mesquita, Pedro M. M., Wilson, Sarah S., Manlow, Philippe, Fischetti, Lucia, Keller, Marla J., Herold, Betsy C., Shattock, Robin J. |
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| description | <jats:title>ABSTRACT</jats:title> <jats:p> A structurally novel candidate microbicide, PPCM, which is formed from the reaction of <jats:sc>d,l</jats:sc> -mandelic acid with sulfuric acid, provides activity against human immunodeficiency virus (HIV) and herpes simplex virus (HSV) and is not cytotoxic. The objectives of the current studies were to comprehensively evaluate the activity of PPCM in cell and explant cultures, explore the possibility of combining PPCM with HIV-specific reverse transcriptase inhibitors, and evaluate the efficacy of a formulated gel against genital herpes in a murine model. PPCM inhibited infection by laboratory and clinical R5 and X4 clade B and clade C HIV strains in cell culture. Ectocervical and endocervical tissue explants exposed to HIV-1 <jats:sub>BaL</jats:sub> in the presence of PPCM were protected (50% inhibitory concentrations [IC <jats:sub>50</jats:sub> ] of 3.9 μg/ml for ectocervix and 3.1 μg/ml for endocervix), and transfer of virus to target T cells via migratory cells was significantly impaired (IC <jats:sub>50</jats:sub> of 35.7 μg/ml for ectocervix and 54.6 μg/ml for endocervix). The drug also blocked infection by cell-associated virus. Combinations of PPCM with UC-781 or PMPA in vitro exhibited additive anti-HIV activity. PPCM was incorporated into stable, low-pH gel formulations at concentrations of 0.4% and 4%. Both gels prevented genital herpesvirus infection in mice, even when virus was introduced in human seminal plasma. The abilities of PPCM to inhibit primary HIV isolates, reduce infection by cell-associated virus, and transfer of HIV from migratory to T cells, combined with the complete protection provided by formulated gel against genital herpes, indicate that this drug is an excellent candidate for inclusion in a combination microbicide and would provide protection against both HIV and HSV. </jats:p> |
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| imprint | American Society for Microbiology, 2008 |
| imprint_str_mv | American Society for Microbiology, 2008 |
| institution | DE-Gla1, DE-Zi4, DE-15, DE-Pl11, DE-Rs1, DE-105, DE-14, DE-Ch1, DE-L229, DE-D275, DE-Bn3, DE-Brt1, DE-Zwi2, DE-D161 |
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| physical | 6576-6584 |
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| spelling | Mesquita, Pedro M. M. Wilson, Sarah S. Manlow, Philippe Fischetti, Lucia Keller, Marla J. Herold, Betsy C. Shattock, Robin J. 0022-538X 1098-5514 American Society for Microbiology Virology Insect Science Immunology Microbiology http://dx.doi.org/10.1128/jvi.00335-08 <jats:title>ABSTRACT</jats:title> <jats:p> A structurally novel candidate microbicide, PPCM, which is formed from the reaction of <jats:sc>d,l</jats:sc> -mandelic acid with sulfuric acid, provides activity against human immunodeficiency virus (HIV) and herpes simplex virus (HSV) and is not cytotoxic. The objectives of the current studies were to comprehensively evaluate the activity of PPCM in cell and explant cultures, explore the possibility of combining PPCM with HIV-specific reverse transcriptase inhibitors, and evaluate the efficacy of a formulated gel against genital herpes in a murine model. PPCM inhibited infection by laboratory and clinical R5 and X4 clade B and clade C HIV strains in cell culture. Ectocervical and endocervical tissue explants exposed to HIV-1 <jats:sub>BaL</jats:sub> in the presence of PPCM were protected (50% inhibitory concentrations [IC <jats:sub>50</jats:sub> ] of 3.9 μg/ml for ectocervix and 3.1 μg/ml for endocervix), and transfer of virus to target T cells via migratory cells was significantly impaired (IC <jats:sub>50</jats:sub> of 35.7 μg/ml for ectocervix and 54.6 μg/ml for endocervix). The drug also blocked infection by cell-associated virus. Combinations of PPCM with UC-781 or PMPA in vitro exhibited additive anti-HIV activity. PPCM was incorporated into stable, low-pH gel formulations at concentrations of 0.4% and 4%. Both gels prevented genital herpesvirus infection in mice, even when virus was introduced in human seminal plasma. The abilities of PPCM to inhibit primary HIV isolates, reduce infection by cell-associated virus, and transfer of HIV from migratory to T cells, combined with the complete protection provided by formulated gel against genital herpes, indicate that this drug is an excellent candidate for inclusion in a combination microbicide and would provide protection against both HIV and HSV. </jats:p> Candidate Microbicide PPCM Blocks Human Immunodeficiency Virus Type 1 Infection in Cell and Tissue Cultures and Prevents Genital Herpes in a Murine Model Journal of Virology |
| spellingShingle | Mesquita, Pedro M. M., Wilson, Sarah S., Manlow, Philippe, Fischetti, Lucia, Keller, Marla J., Herold, Betsy C., Shattock, Robin J., Journal of Virology, Candidate Microbicide PPCM Blocks Human Immunodeficiency Virus Type 1 Infection in Cell and Tissue Cultures and Prevents Genital Herpes in a Murine Model, Virology, Insect Science, Immunology, Microbiology |
| title | Candidate Microbicide PPCM Blocks Human Immunodeficiency Virus Type 1 Infection in Cell and Tissue Cultures and Prevents Genital Herpes in a Murine Model |
| title_full | Candidate Microbicide PPCM Blocks Human Immunodeficiency Virus Type 1 Infection in Cell and Tissue Cultures and Prevents Genital Herpes in a Murine Model |
| title_fullStr | Candidate Microbicide PPCM Blocks Human Immunodeficiency Virus Type 1 Infection in Cell and Tissue Cultures and Prevents Genital Herpes in a Murine Model |
| title_full_unstemmed | Candidate Microbicide PPCM Blocks Human Immunodeficiency Virus Type 1 Infection in Cell and Tissue Cultures and Prevents Genital Herpes in a Murine Model |
| title_short | Candidate Microbicide PPCM Blocks Human Immunodeficiency Virus Type 1 Infection in Cell and Tissue Cultures and Prevents Genital Herpes in a Murine Model |
| title_sort | candidate microbicide ppcm blocks human immunodeficiency virus type 1 infection in cell and tissue cultures and prevents genital herpes in a murine model |
| title_unstemmed | Candidate Microbicide PPCM Blocks Human Immunodeficiency Virus Type 1 Infection in Cell and Tissue Cultures and Prevents Genital Herpes in a Murine Model |
| topic | Virology, Insect Science, Immunology, Microbiology |
| url | http://dx.doi.org/10.1128/jvi.00335-08 |