PMC9478384_01
Dynamics of immunological, microbial, and behavioral variables of productive HSV-2 and HPV coinfection in Case A. (A:) Per cell viral loads (log). The color indicates the virus genotype (or species) and the shape the type of sample. (B:) Shannon diversity index. (C:) Abundance and diversity of the main bacterial species found in the vaginal microbiota communities. Colors indicate different species, numbers above the bars indicate the percentage of reads attributed to that species. "g" refers to bacteria for which we can only identify the genera level and not the precise species. Only species with a normalized abundance greater than 5 % are shown. (D:) Community State Types (CST) dynamics. (E:) Circulating IgG and IgM antibody titers. Colors indicate different antibodies and corresponding dashed lines indicate the threshold values for each antibody. (F) Cytokines local concentrations. Colors show different cytokines. (G) Self-reported stress levels. (H) Vaginal pH measures. (I) Self-reported menstruation within the last week. (J) Self-reported occurrence of a new sexual partner during the last week. (K) self-reported sexual intercourse with vaginal penetration during the last week. Red bars indicate a yes answer to the question. In panels A, E, and F lines were obtained by fitting a spline curve. The data is shown per day of follow-up (DoF).
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This was followed by an absence of detection for 100 days (Fig. 1A). Furthermore, after HSV-2 clearance, HPV31 virus load steadily decreased by one order of magnitude in 150 days to approximately 2.7 x 104 copies per cell (Fig. 1A). At inclusion, the vaginal microbiota was mainly dominated by Lactobacillus iners with a minority of Lactobacillus jensenii (Fig. 1C, and D). The microbial diversity, characterized by the Shannon index, was also higher during the reactivation (Fig. 1B). We lack microbiota data between the two HSV-2 reactivation events but we can detect elevated vaginal pH levels (above 4.5), which could indicate variations in CSTs (Fig. 1H). The last two detections of HSV-2 DNA and the onset of HPV66 infection (at DoF 168 and 182) coincided with a shift to CST III with a dominance of Lactobacillus iners (Fig. 1A, C, and D). The threshold for seropositivity for each antibody type is shown with a dashed line in Fig. 1E. Since the detailed follow-up does not point to any specific event, this could be attributed to an issue with this particular sample (Fig. 1F). On the other hand, the reporting of a new sexual partner on DoF 164 and sexual intercourse on DoF 143 and 168 coincided with the acquisition of HPV66 (Fig. 1G, J and K).
PMC9478384_02
Dynamics of immunological, microbial, and behavioral variables of productive HSV-2 and HPV coinfection in Case B. See Fig. 1 for details about the figure contents.
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Although she was seropositive for HSV-2, she did not report any past symptoms of the infection (Fig. 2E). We observed an HSV-2 reactivation at DoF 126 that was followed by two samples with increasing viral loads at DoF 154 and 217 (Fig. 2A)). Finally, the end of the HSV-2 reactivation event and of the HPV52 infection appeared to occur simultaneously (Fig. 2A). Case B had a vaginal microbiota dominated by Lactobacillus iners (i.e. CST III, Fig. 2C and D) with rather elevated values of vaginal pH (Fig. 2G). CST, i.e. CST I, which was followed by a shift to CST V, but with a high abundance of Gardnerella vaginalis (Fig. 2A and C). On the immunological side, the most striking patterns were a peak in anti-HV52 IgG on DoF 210 and IgM on DoF 273 that is right before and right after HPV52 clearance (Fig. 2E). This could be related to her low virus load not triggering a strong immune response (Fig. 2E). As for Case B, she reported elevated stress levels for three weeks in a row just before the HSV-2 reactivation episode (Fig. 2F). She also reported a new partner on DoF 95 and 154, that is right before and right after the HSV-2 reactivation episode, and reported having sexual intercourse on DoF 77, before HSV-2 reactivation on DoF 126 (Fig. 2I). She also reported a new partner on DoF 154, right after the HSV-2 reactivation Fig. 2F, I and J).