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Comparative Study
, 28 (1), 76-81

A Comparison of Lower Genital Tract Glycogen and Lactic Acid Levels in Women and Macaques: Implications for HIV and SIV Susceptibility

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Comparative Study

A Comparison of Lower Genital Tract Glycogen and Lactic Acid Levels in Women and Macaques: Implications for HIV and SIV Susceptibility

Paria Mirmonsef et al. AIDS Res Hum Retroviruses.

Abstract

Understanding factors that affect heterosexual transmission of HIV in women is of great importance. Lactobacilli in the lower genital tract of women utilize glycogen in vaginal epithelial cells as an energy source and produce lactic acid. The resultant vaginal acidity is believed to provide protection against HIV infection. Conversely, bacterial vaginosis (BV) is characterized by less lactic acid and a higher pH, and is associated with increased susceptibility to HIV infection. Because vaginal infection of macaques with simian immunodeficiency virus (SIV) or simian-human immunodeficiency virus (SHIV) is used as a model to study HIV sexual transmission, and because previous studies have shown a paucity of lactobacilli in rhesus macaques' lower genital tract, we compared lactic acid and glycogen levels in the genital fluid of rhesus and pigtail macaques with levels found in humans. The levels of lactic acid were lower in both rhesus (median=1.2 mol lactate/mg protein) and pigtail macaques (median=0.7 mol/mg) compared to women with healthy genital microbiota (median=4.2 mol/mg). Glycogen levels were significantly lower in both rhesus (median=0.004 μg glycogen/μg protein) and pigtail macaques (median=0 μg/μg) than in women (median=0.2 μg/μg). No significant differences in glycogen or lactate levels were observed comparing longitudinally collected samples from cycling pigtail macaques. These data show that the previously reported scarcity of lactobacilli in macaques correlates with low glycogen and lactic acid levels. These findings have important implications for studies of vaginal infection of macaques with SIV or SHIV and further our understanding of how the bacterial microbiota influences HIV infection.

Figures

FIG. 1.
FIG. 1.
Lactate:protein levels in women and macaques. Cervical-vaginal lavage (CVL) samples from 25 human subjects and 23 rhesus and 18 pigtail macaques were collected as described in Materials and Methods. Some macaques were assessed more than once. Lactate and protein levels were measured per manufacturer's instructions. The two-tailed p-values were calculated using the Dunn's Multiple Comparisons post test. Bacterial vaginosis (BV) in women was determined by Nugent Gram stain values of 7–10, while non-BV was 0–6. No significant differences were found in humans with BV compared to rhesus or pigtail macaques.
FIG. 2.
FIG. 2.
Glycogen:protein levels in woman and macaques. CVL samples were collected as described above (Fig. 1 and Materials and Methods). Glycogen and protein levels were measured per manufacturer's instructions. The two-tailed p-values were calculated using the Mood's Median test. As in Fig. 1, BV in women was determined by Nugent Gram stain values of 7–10, while non-BV was 0–6. Glycogen:protein levels in macaques were significantly lower than in women without BV (p<0.001, Mood's Median test), but were omitted from the figure for the sake of clarity.
FIG. 3.
FIG. 3.
Lactate and glycogen levels collected over the menstrual cycle in pigtail macaques. CVL samples were collected as described in Materials and Methods. Lactate (a) and glycogen (b) levels were measured per manufacturer's instructions and standardized to protein levels as described in Materials and Methods. The two-tailed p-values were calculated using Dunn's Multiple Comparisons post test and a p-value<0.05 was considered to be significant.
FIG. 4.
FIG. 4.
Lactate:protein and glycogen:protein levels at different stages of menstrual cycle. CVL samples were collected and lactate (a) and glycogen (b) levels were measured and standardized to protein levels as described. Plasma progesterone concentrations were measured as described in Materials and Methods. The two-tailed p-value was calculated using the Dunn's Multiple Comparisons post test. No significant differences were observed among the three groups.

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