Glycerol Monolaurate, an Analogue to a Factor Secreted by <italic toggle="yes">Lactobacillus</italic>, Is Virucidal against Enveloped Viruses, Including HIV-1
ABSTRACT The vaginal microbiota influences sexual transmission of human immunodeficiency virus type 1 (HIV-1). Colonization of the vaginal tract is normally dominated by Lactobacillus species. Both Lactobacillus and Enterococcus faecalis may secrete reutericyclin, which inhibits the growth of a vari...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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American Society for Microbiology
2020-06-01
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| Series: | mBio |
| Subjects: | |
| Online Access: | https://journals.asm.org/doi/10.1128/mBio.00686-20 |
| _version_ | 1818856675041345536 |
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| author | Jennifer L. Welch Jinhua Xiang Chioma M. Okeoma Patrick M. Schlievert Jack T. Stapleton |
| author_facet | Jennifer L. Welch Jinhua Xiang Chioma M. Okeoma Patrick M. Schlievert Jack T. Stapleton |
| author_sort | Jennifer L. Welch |
| collection | DOAJ |
| description | ABSTRACT The vaginal microbiota influences sexual transmission of human immunodeficiency virus type 1 (HIV-1). Colonization of the vaginal tract is normally dominated by Lactobacillus species. Both Lactobacillus and Enterococcus faecalis may secrete reutericyclin, which inhibits the growth of a variety of pathogenic bacteria. Increasing evidence suggests a potential therapeutic role for an analogue of reutericyclin, glycerol monolaurate (GML), against microbial pathogens. Previous studies using a macaque vaginal simian immunodeficiency virus (SIV) transmission model demonstrated that GML reduces transmission and alters immune responses to infection in vitro. Previous studies showed that structural analogues of GML negatively impact other enveloped viruses. We sought to expand understanding of how GML inhibits HIV-1 and other enveloped viruses and show that GML restricts HIV-1 entry post-CD4 engagement at the step of coreceptor binding. Further, HIV-1 and yellow fever virus (YFV) particles were more sensitive to GML interference than particles “matured” by proteolytic processing. We show that high-pressure-liquid-chromatography (HPLC)-purified reutericyclin and reutericyclin secreted by Lactobacillus inhibit HIV-1. These data emphasize the importance and protective nature of the normal vaginal flora during viral infections and provide insights into the antiviral mechanism of GML during HIV-1 infection and, more broadly, to other enveloped viruses. IMPORTANCE A total of 340 million sexually transmitted infections (STIs) are acquired each year. Antimicrobial agents that target multiple infectious pathogens are ideal candidates to reduce the number of newly acquired STIs. The antimicrobial and immunoregulatory properties of GML make it an excellent candidate to fit this critical need. Previous studies established the safety profile and antibacterial activity of GML against both Gram-positive and Gram-negative bacteria. GML protected against high-dose SIV infection and reduced inflammation, which can exacerbate disease, during infection. We found that GML inhibits HIV-1 and other human-pathogenic viruses (yellow fever virus, mumps virus, and Zika virus), broadening its antimicrobial range. Because GML targets diverse infectious pathogens, GML may be an effective agent against the broad range of sexually transmitted pathogens. Further, our data show that reutericyclin, a GML analog expressed by some lactobacillus species, also inhibits HIV-1 replication and thus may contribute to the protective effect of Lactobacillus in HIV-1 transmission. |
| first_indexed | 2024-12-19T08:28:16Z |
| format | Article |
| id | doaj.art-57159630436f46228a167a5f2ac212d0 |
| institution | Directory Open Access Journal |
| issn | 2150-7511 |
| language | English |
| last_indexed | 2024-12-19T08:28:16Z |
| publishDate | 2020-06-01 |
| publisher | American Society for Microbiology |
| record_format | Article |
| series | mBio |
| spelling | doaj.art-57159630436f46228a167a5f2ac212d02022-12-21T20:29:15ZengAmerican Society for MicrobiologymBio2150-75112020-06-0111310.1128/mBio.00686-20Glycerol Monolaurate, an Analogue to a Factor Secreted by <italic toggle="yes">Lactobacillus</italic>, Is Virucidal against Enveloped Viruses, Including HIV-1Jennifer L. Welch0Jinhua Xiang1Chioma M. Okeoma2Patrick M. Schlievert3Jack T. Stapleton4Department of Microbiology and Immunology, Carver College of Medicine, University of Iowa, Iowa City, Iowa, USADepartment of Microbiology and Immunology, Carver College of Medicine, University of Iowa, Iowa City, Iowa, USADepartment of Pharmacology, Stony Brook University School of Medicine, Stony Brook, New York, USADepartment of Microbiology and Immunology, Carver College of Medicine, University of Iowa, Iowa City, Iowa, USADepartment of Microbiology and Immunology, Carver College of Medicine, University of Iowa, Iowa City, Iowa, USAABSTRACT The vaginal microbiota influences sexual transmission of human immunodeficiency virus type 1 (HIV-1). Colonization of the vaginal tract is normally dominated by Lactobacillus species. Both Lactobacillus and Enterococcus faecalis may secrete reutericyclin, which inhibits the growth of a variety of pathogenic bacteria. Increasing evidence suggests a potential therapeutic role for an analogue of reutericyclin, glycerol monolaurate (GML), against microbial pathogens. Previous studies using a macaque vaginal simian immunodeficiency virus (SIV) transmission model demonstrated that GML reduces transmission and alters immune responses to infection in vitro. Previous studies showed that structural analogues of GML negatively impact other enveloped viruses. We sought to expand understanding of how GML inhibits HIV-1 and other enveloped viruses and show that GML restricts HIV-1 entry post-CD4 engagement at the step of coreceptor binding. Further, HIV-1 and yellow fever virus (YFV) particles were more sensitive to GML interference than particles “matured” by proteolytic processing. We show that high-pressure-liquid-chromatography (HPLC)-purified reutericyclin and reutericyclin secreted by Lactobacillus inhibit HIV-1. These data emphasize the importance and protective nature of the normal vaginal flora during viral infections and provide insights into the antiviral mechanism of GML during HIV-1 infection and, more broadly, to other enveloped viruses. IMPORTANCE A total of 340 million sexually transmitted infections (STIs) are acquired each year. Antimicrobial agents that target multiple infectious pathogens are ideal candidates to reduce the number of newly acquired STIs. The antimicrobial and immunoregulatory properties of GML make it an excellent candidate to fit this critical need. Previous studies established the safety profile and antibacterial activity of GML against both Gram-positive and Gram-negative bacteria. GML protected against high-dose SIV infection and reduced inflammation, which can exacerbate disease, during infection. We found that GML inhibits HIV-1 and other human-pathogenic viruses (yellow fever virus, mumps virus, and Zika virus), broadening its antimicrobial range. Because GML targets diverse infectious pathogens, GML may be an effective agent against the broad range of sexually transmitted pathogens. Further, our data show that reutericyclin, a GML analog expressed by some lactobacillus species, also inhibits HIV-1 replication and thus may contribute to the protective effect of Lactobacillus in HIV-1 transmission.https://journals.asm.org/doi/10.1128/mBio.00686-20coronavirusglycerol monolaurateLactobacillusmumps virusreutericyclinviruses |
| spellingShingle | Jennifer L. Welch Jinhua Xiang Chioma M. Okeoma Patrick M. Schlievert Jack T. Stapleton Glycerol Monolaurate, an Analogue to a Factor Secreted by <italic toggle="yes">Lactobacillus</italic>, Is Virucidal against Enveloped Viruses, Including HIV-1 mBio coronavirus glycerol monolaurate Lactobacillus mumps virus reutericyclin viruses |
| title | Glycerol Monolaurate, an Analogue to a Factor Secreted by <italic toggle="yes">Lactobacillus</italic>, Is Virucidal against Enveloped Viruses, Including HIV-1 |
| title_full | Glycerol Monolaurate, an Analogue to a Factor Secreted by <italic toggle="yes">Lactobacillus</italic>, Is Virucidal against Enveloped Viruses, Including HIV-1 |
| title_fullStr | Glycerol Monolaurate, an Analogue to a Factor Secreted by <italic toggle="yes">Lactobacillus</italic>, Is Virucidal against Enveloped Viruses, Including HIV-1 |
| title_full_unstemmed | Glycerol Monolaurate, an Analogue to a Factor Secreted by <italic toggle="yes">Lactobacillus</italic>, Is Virucidal against Enveloped Viruses, Including HIV-1 |
| title_short | Glycerol Monolaurate, an Analogue to a Factor Secreted by <italic toggle="yes">Lactobacillus</italic>, Is Virucidal against Enveloped Viruses, Including HIV-1 |
| title_sort | glycerol monolaurate an analogue to a factor secreted by italic toggle yes lactobacillus italic is virucidal against enveloped viruses including hiv 1 |
| topic | coronavirus glycerol monolaurate Lactobacillus mumps virus reutericyclin viruses |
| url | https://journals.asm.org/doi/10.1128/mBio.00686-20 |
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