CoChat
Sign Up
Cited by 215Reproductive tract infections researchHIV/AIDS Research and InterventionsCervical Cancer and HPV Research

The DOI matches its Crossref record; 49 of the 49 references it cites were found in a registry or an index.

Enhanced Trapping of HIV-1 by Human Cervicovaginal Mucus Is Associated with Lactobacillus crispatus-Dominant Microbiota

Open access
Nunn, Kenetta L., Wang, Ying-Ying, Harit, Dimple, Humphrys, Michael S., Ma, Bing, Cone, Richard, Ravel, Jacques, Lai, Samuel K.·2015·mBio
DOI 10.1128/mbio.01084-15PMC PMC4611035
Open this paper in CoChat — free account

Abstract

UNLABELLED: Cervicovaginal mucus (CVM) can provide a barrier that precludes HIV and other sexually transmitted virions from reaching target cells in the vaginal epithelium, thereby preventing or reducing infections. However, the barrier properties of CVM differ from woman to woman, and the causes of these variations are not yet well understood. Using high-resolution particle tracking of fluorescent HIV-1 pseudoviruses, we found that neither pH nor Nugent scores nor total lactic acid levels correlated significantly with virus trapping in unmodified CVM from diverse donors. Surprisingly, HIV-1 was generally trapped in CVM with relatively high concentrations of d-lactic acid and a Lactobacillus crispatus-dominant microbiota. In contrast, a substantial fraction of HIV-1 virions diffused rapidly through CVM with low concentrations of d-lactic acid that had a Lactobacillus iners-dominant microbiota or significant amounts of Gardnerella vaginalis, a bacterium associated with bacterial vaginosis. Our results demonstrate that the vaginal microbiota, including specific species of Lactobacillus, can alter the diffusional barrier properties of CVM against HIV and likely other sexually transmitted viruses and that these microbiota-associated changes may account in part for the elevated risks of HIV acquisition linked to bacterial vaginosis or intermediate vaginal microbiota. IMPORTANCE: Variations in the vaginal microbiota, especially shifts away from Lactobacillus-dominant microbiota, are associated with differential risks of acquiring HIV or other sexually transmitted infections. However, emerging evidence suggests that Lactobacillus iners frequently colonizes women with recurring bacterial vaginosis, raising the possibility that L. iners may not be as protective as other Lactobacillus species. Our study was designed to improve understanding of how the cervicovaginal mucus barrier against HIV may vary between women along with the vaginal microbiota and led to the finding that the vaginal microbiota, including specific species of Lactobacillus, can directly alter the diffusional barrier properties of cervicovaginal mucus. This work advances our understanding of the complex barrier properties of mucus and highlights the differential protective ability of different species of Lactobacillus, with Lactobacillus crispatus and possibly other species playing a key role in protection against HIV and other sexually transmitted infections. These findings could lead to the development of novel strategies to protect women against HIV.

Overview

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1128/mbio.01084-15

Cites

49 of 49 references verified0 citation errors · 0 not checkable

Statistics

Figures

FIG 1 (A) Representative traces of mobile versus trapped HIV-1 virions compared to PS-PEG nanoparticles that are mucoinert and readily diffuse through CVM and compared to PS-COOH nanoparticles that are mucoadhesive and trapped in CVM. (B to G) HIV-1 mobility measured by average effective diffusivity (Deff) (B to D) values or fraction of mobile virions (E to G) versus pH (B and E), Nugent score (C and F), or total LA (D and G) for n = 31 CVM samples with a pH level of >4.2 (n = 12) or ≤4.2 (n = 19). Dashed lines indicate the cutoff between samples with a significant mobile HIV-1 population (≥10% mobile) and those in which HIV-1 is largely trapped (<10% mobile). w/v, weight/volume.
FIG 1 (A) Representative traces of mobile versus trapped HIV-1 virions compared to PS-PEG nanoparticles that are mucoinert and readily diffuse through CVM and compared to PS-COOH nanoparticles that are mucoadhesive and trapped in CVM. (B to G) HIV-1 mobility measured by average effective diffusivity (Deff) (B to D) values or fraction of mobile virions (E to G) versus pH (B and E), Nugent score (C and F), or total LA (D and G) for n = 31 CVM samples with a pH level of >4.2 (n = 12) or ≤4.2 (n = 19). Dashed lines indicate the cutoff between samples with a significant mobile HIV-1 population (≥10% mobile) and those in which HIV-1 is largely trapped (<10% mobile). w/v, weight/volume.CC BY-NC-SA · PubMed Central
FIG 2 HIV-1 mobility measured by average effective diffusivity (Deff) (A to C) values or fraction of mobile virions (D to F) versus D-LA (A and D), L-LA (B and E), or D:L ratio (C and F) for n = 31 CVM samples with a pH level of >4.2 (n = 12) or ≤4.2 (n = 19). Dashed lines indicate the cutoff between samples with a significant mobile HIV-1 population (≥10% mobile) and those in which HIV-1 is largely trapped (<10% mobile).
FIG 2 HIV-1 mobility measured by average effective diffusivity (Deff) (A to C) values or fraction of mobile virions (D to F) versus D-LA (A and D), L-LA (B and E), or D:L ratio (C and F) for n = 31 CVM samples with a pH level of >4.2 (n = 12) or ≤4.2 (n = 19). Dashed lines indicate the cutoff between samples with a significant mobile HIV-1 population (≥10% mobile) and those in which HIV-1 is largely trapped (<10% mobile).CC BY-NC-SA · PubMed Central
FIG 3 (A) 16S rRNA sequencing and RNAseq analysis of CVM specimens reveals groups with distinct vaginal microbiotas: L. crispatus-dominant microbiota (group 1), L. iners-dominant microbiota (group 2), and microbiota containing a significant fraction of G. vaginalis (group 3). The color bar indicates the abundance of different bacterial species as a proportion of all species in the sample. Annulus charts depict the average distributions of the bacterial population across species of lactobacilli, Gardnerella vaginalis, and other species within each group. Donor identification numbers (IDs) are indicated to allow comparisons to the biochemical characterization data and bacterial abundance values in Tables S1 and S2 in the supplemental material. (B) HIV-1 mobility measured by average effective diffusivity (Deff) values or fraction of mobile virions in CVM samples within each group. The dashed line indicates the cutoff between samples with a significant mobile HIV-1 population (≥10% mobile) and those in which HIV-1 is largely trapped (<10% mobile). (C) Average pH, Nugent score, total LA, D-LA, L-LA, and D:L ratio for CVM samples within each group. *, P < 0.05 (statistically significant difference between group 1 and groups 2 and 3).
FIG 3 (A) 16S rRNA sequencing and RNAseq analysis of CVM specimens reveals groups with distinct vaginal microbiotas: L. crispatus-dominant microbiota (group 1), L. iners-dominant microbiota (group 2), and microbiota containing a significant fraction of G. vaginalis (group 3). The color bar indicates the abundance of different bacterial species as a proportion of all species in the sample. Annulus charts depict the average distributions of the bacterial population across species of lactobacilli, Gardnerella vaginalis, and other species within each group. Donor identification numbers (IDs) are indicated to allow comparisons to the biochemical characterization data and bacterial abundance values in Tables S1 and S2 in the supplemental material. (B) HIV-1 mobility measured by average effective diffusivity (Deff) values or fraction of mobile virions in CVM samples within each group. The dashed line indicates the cutoff between samples with a significant mobile HIV-1 population (≥10% mobile) and those in which HIV-1 is largely trapped (<10% mobile). (C) Average pH, Nugent score, total LA, D-LA, L-LA, and D:L ratio for CVM samples within each group. *, P < 0.05 (statistically significant difference between group 1 and groups 2 and 3).CC BY-NC-SA · PubMed Central
FIG 4 Comparison of average effective diffusivity (Deff) values for mucoinert synthetic beads (PS-PEG) (A), HIV-1 ΔEnv pseudovirus (B), or PS-COOH (C) to that of HIV-1 in native CVM. Data represent n = 8, 13, and 8 distinct CVM samples for PS-PEG, HIV-1 ΔEnv, and PS-COOH, respectively. Lines connect pairs of data points for the same sample.
FIG 4 Comparison of average effective diffusivity (Deff) values for mucoinert synthetic beads (PS-PEG) (A), HIV-1 ΔEnv pseudovirus (B), or PS-COOH (C) to that of HIV-1 in native CVM. Data represent n = 8, 13, and 8 distinct CVM samples for PS-PEG, HIV-1 ΔEnv, and PS-COOH, respectively. Lines connect pairs of data points for the same sample.CC BY-NC-SA · PubMed Central
FIG 5 Comparison of average effective diffusivity values for HIV-1 in native versus neutralized (pH 7) CVM. Data represent n = 31 distinct CVM samples. Lines connect pairs of data points for the same sample.
FIG 5 Comparison of average effective diffusivity values for HIV-1 in native versus neutralized (pH 7) CVM. Data represent n = 31 distinct CVM samples. Lines connect pairs of data points for the same sample.CC BY-NC-SA · PubMed Central

Verification

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Citations

Cites

Show all 49 references

Cited by

Sorted by citations

Related

See all

Metadata

Authors
Nunn, K. L., Wang, Y.-Y., Harit, D., Humphrys, M. S., Ma, B., Cone, R., Ravel, J., & Lai, S. K.
Affiliations
  • University of North Carolina at Chapel Hill (US)
  • Department of Biophysics, Johns Hopkins University, Baltimore, Maryland, USA
  • University of Maryland, Baltimore (US)
  • Johns Hopkins University (US)
Corresponding author
Lai, Samuel K.
ORCID
Venue
mBio
Publisher
American Society for Microbiology
Published
2015-10-30
Volume
6
Issue
5
Pages
e01084-15
ISSN
  • 2150-7511 (ISSN-L)
  • 2161-2129
DOI
10.1128/mbio.01084-15
PMC
PMC4611035
OpenAlex
W2172682788
Cited by
194
References
49
Citations by year
2026: 8 · 2025: 10 · 2024: 13 · 2023: 17 · 2022: 24 · 2021: 34 · 2020: 18 · 2019: 17 · 2018: 22 · 2017: 16 · 2016: 12 · 2015: 3
FWCI
14.89
Type
journal article
Language
en
Open access
Licence
Locations
  • mBio (publishedVersion, cc-by-nc-sa)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-sa)
  • PubMed Central (publishedVersion, cc-by-nc-sa)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • National Institutes of Health (1f32ai102535-01)
  • University of North Carolina at Chapel Hill
  • National Institute of General Medical Sciences (R25GM089569)
  • National Institute of Allergy and Infectious Diseases (U19AI084044, R21AI093242, F32 AI102535, U19AI096398, P30 AI50410, 1F32AI102535, P30AI050410)
Topics
  • Life Sciences › Immunology and Microbiology › Microbiology › Reproductive tract infections research
  • Health Sciences › Medicine › Infectious Diseases › HIV/AIDS Research and Interventions
  • Health Sciences › Medicine › Epidemiology › Cervical Cancer and HPV Research
Keywords
HIV-1, cervicovaginal mucus, vaginal microbiota, Lactobacillus crispatus, Lactobacillus iners, Gardnerella vaginalis, bacterial vaginosis, mucus barrier, virus trapping, D-lactate, HIV acquisition, sexually transmitted infections, particle tracking
MeSH terms
Adult, Cervix Uteri, Female, Gardnerella vaginalis, Humans, Hydrogen-Ion Concentration, Lactobacillus, Mucus, Vagina, HIV-1, Lactic Acid, Young Adult

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review