Characterization of the Genital Microenvironment of Female Rhesus Macaques Prior to and After SIV Infection

Overview

Journal Am J Reprod Immunol

Specialties Allergy & Immunology
Reproductive Medicine

Date 2015 Aug 21

PMID 26290147

Citations 2

Authors

Whitney A Nichols

Leslie Birke

Jason Dufour

Nisha Loganantharaj

Gregory J Bagby

Steve Nelson

Patricia E Molina

Angela M Amedee

Affiliations

Soon will be listed here.

Abstract

Problem: HIV infection among women is frequently modeled in female rhesus macaques. Longitudinal studies on genital compartment and hormonal factors that can influence susceptibility to SIV infection are lacking in this animal model.

Method Of Study: Genital specimens and menstruation of indoor-housed female rhesus macaques were analyzed prior to and after SIV infection.

Results: Median menstrual cycle length averaged 27 days, although highly variable cycle lengths and frequent periods of amenorrhea were observed during summer months. The vaginal microbiota, characterized by adapted Nugent scoring, showed predominance of small Gram-variable rods and Gram-positive cocci. Highly variable vaginal cytokine levels were observed pre- and post-SIV infection. Vaginal viral loads correlated with plasma viral loads, but were not associated with progesterone levels.

Conclusion: These results provide an integrated characterization of important factors in the vaginal microenvironment that are relevant to the experimental design of HIV prevention and transmission studies in female rhesus macaques.

Citing Articles

High-Resolution Quantitative Mapping of Macaque Cervicovaginal Epithelial Thickness: Implications for Mucosal Vaccine Delivery.

Vincent K, Frost P, Motamedi M, Dick Jr E, Wei J, Yang J Front Immunol. 2021; 12:660524.

PMID: 34262561 PMC: 8273733. DOI: 10.3389/fimmu.2021.660524.

An intravaginal ring that releases three antiviral agents and a contraceptive blocks SHIV-RT infection, reduces HSV-2 shedding, and suppresses hormonal cycling in rhesus macaques.

Derby N, Aravantinou M, Kenney J, Ugaonkar S, Wesenberg A, Wilk J Drug Deliv Transl Res. 2017; 7(6):840-858.

PMID: 28600625 PMC: 5656733. DOI: 10.1007/s13346-017-0389-0.

References

Martin H, Richardson B, Nyange P, Lavreys L, Hillier S, Chohan B . Vaginal lactobacilli, microbial flora, and risk of human immunodeficiency virus type 1 and sexually transmitted disease acquisition. J Infect Dis. 1999; 180(6):1863-8. DOI: 10.1086/315127. View

Smith S, Baskin G, Marx P . Estrogen protects against vaginal transmission of simian immunodeficiency virus. J Infect Dis. 2000; 182(3):708-15. DOI: 10.1086/315776. View

Villanueva J, Ellerbrock T, Lennox J, Bush T, Wright T, Evans-Strickfaden T . The menstrual cycle does not affect human immunodeficiency virus type 1 levels in vaginal secretions. J Infect Dis. 2002; 185(2):170-7. DOI: 10.1086/338447. View

Buse E, Habermann G, Osterburg I, Korte R, Weinbauer G . Reproductive/developmental toxicity and immunotoxicity assessment in the nonhuman primate model. Toxicology. 2003; 185(3):221-7. DOI: 10.1016/s0300-483x(02)00614-5. View

Abel K, Compton L, Rourke T, Montefiori D, Lu D, Rothaeusler K . Simian-human immunodeficiency virus SHIV89.6-induced protection against intravaginal challenge with pathogenic SIVmac239 is independent of the route of immunization and is associated with a combination of cytotoxic T-lymphocyte and alpha interferon.... J Virol. 2003; 77(5):3099-118. PMC: 149756. DOI: 10.1128/jvi.77.5.3099-3118.2003. View

Kaushic C, Ashkar A, Reid L, Rosenthal K . Progesterone increases susceptibility and decreases immune responses to genital herpes infection. J Virol. 2003; 77(8):4558-65. PMC: 152159. DOI: 10.1128/jvi.77.8.4558-4565.2003. View

Beagley K, Gockel C . Regulation of innate and adaptive immunity by the female sex hormones oestradiol and progesterone. FEMS Immunol Med Microbiol. 2003; 38(1):13-22. DOI: 10.1016/S0928-8244(03)00202-5. View

Castle P, Rodriguez A, Bowman F, Herrero R, Schiffman M, Bratti M . Comparison of ophthalmic sponges for measurements of immune markers from cervical secretions. Clin Diagn Lab Immunol. 2004; 11(2):399-405. PMC: 371211. DOI: 10.1128/cdli.11.2.399-405.2004. View

Galvin S, Cohen M . The role of sexually transmitted diseases in HIV transmission. Nat Rev Microbiol. 2004; 2(1):33-42. DOI: 10.1038/nrmicro794. View

10.

Spear G, Gilbert D, Sikaroodi M, Doyle L, Green L, Gillevet P . Identification of rhesus macaque genital microbiota by 16S pyrosequencing shows similarities to human bacterial vaginosis: implications for use as an animal model for HIV vaginal infection. AIDS Res Hum Retroviruses. 2010; 26(2):193-200. PMC: 2835387. DOI: 10.1089/aid.2009.0166. View

11.

Haase A . Targeting early infection to prevent HIV-1 mucosal transmission. Nature. 2010; 464(7286):217-23. DOI: 10.1038/nature08757. View

12.

Jespers V, Harandi A, Hinkula J, Medaglini D, Le Grand R, Stahl-Hennig C . Assessment of mucosal immunity to HIV-1. Expert Rev Vaccines. 2010; 9(4):381-94. DOI: 10.1586/erv.10.21. View

13.

Wira C, Fahey J, Ghosh M, Patel M, Hickey D, Ochiel D . Sex hormone regulation of innate immunity in the female reproductive tract: the role of epithelial cells in balancing reproductive potential with protection against sexually transmitted pathogens. Am J Reprod Immunol. 2010; 63(6):544-65. PMC: 3837356. DOI: 10.1111/j.1600-0897.2010.00842.x. View

14.

DU Y, Fan T, Tan Y, Xiong Z, Wang Z . Seasonal changes in the reproductive physiology of female rhesus macaques (Macaca mulatta). J Am Assoc Lab Anim Sci. 2010; 49(3):289-93. PMC: 2877299. View

15.

Veazey R, Ketas T, Dufour J, Moroney-Rasmussen T, Green L, Klasse P . Protection of rhesus macaques from vaginal infection by vaginally delivered maraviroc, an inhibitor of HIV-1 entry via the CCR5 co-receptor. J Infect Dis. 2010; 202(5):739-44. PMC: 2916941. DOI: 10.1086/655661. View

16.

Cu-Uvin S, Delong A, Venkatesh K, Hogan J, Ingersoll J, Kurpewski J . Genital tract HIV-1 RNA shedding among women with below detectable plasma viral load. AIDS. 2010; 24(16):2489-97. DOI: 10.1097/QAD.0b013e32833e5043. View

17.

Thurman A, Doncel G . Innate immunity and inflammatory response to Trichomonas vaginalis and bacterial vaginosis: relationship to HIV acquisition. Am J Reprod Immunol. 2010; 65(2):89-98. DOI: 10.1111/j.1600-0897.2010.00902.x. View

18.

Mirmonsef P, Gilbert D, Zariffard M, Hamaker B, Kaur A, Landay A . The effects of commensal bacteria on innate immune responses in the female genital tract. Am J Reprod Immunol. 2010; 65(3):190-5. PMC: 3581076. DOI: 10.1111/j.1600-0897.2010.00943.x. View

19.

Hickey D, Patel M, Fahey J, Wira C . Innate and adaptive immunity at mucosal surfaces of the female reproductive tract: stratification and integration of immune protection against the transmission of sexually transmitted infections. J Reprod Immunol. 2011; 88(2):185-94. PMC: 3094911. DOI: 10.1016/j.jri.2011.01.005. View

20.

Baeten J, Kahle E, Lingappa J, Coombs R, Delany-Moretlwe S, Nakku-Joloba E . Genital HIV-1 RNA predicts risk of heterosexual HIV-1 transmission. Sci Transl Med. 2011; 3(77):77ra29. PMC: 3087186. DOI: 10.1126/scitranslmed.3001888. View