title: Cataloguing of Potential HIV Susceptibility Factors during the Menstrual Cycle of Pig-Tailed Macaques by Using a Systems Biology Approach.
abstract: Our earlier studies with pig-tailed macaques demonstrated various simian-human immunodeficiency virus (SHIV) susceptibilities during the menstrual cycle, likely caused by cyclic variations in immune responses in the female genital tract. There is concern that high-dose, long-lasting, injectable progestin-based contraception could mimic the high-progesterone luteal phase and predispose women to human immunodeficiency type 1 (HIV-1) acquisition and transmission. In this study, we adopted a systems biology approach employing proteomics (tandem mass spectrometry), transcriptomics (RNA microarray hybridization), and other specific protein assays (enzyme-linked immunosorbent assays and multiplex chemokine and cytokine measurements) to characterize the effects of hormonal changes on the expression of innate factors and secreted proteins in the macaque vagina. Several antiviral factors and pathways (including acute-phase response signaling and complement system) were overexpressed in the follicular phase. Conversely, during the luteal phase there were factors overexpressed (including moesins, syndecans, and integrins, among others) that could play direct or indirect roles in enhancing HIV-1 infection. Thus, our study showed that specific pathways and proteins or genes might work in tandem to regulate innate immunity, thus fostering further investigation and future design of approaches to help counter HIV-1 acquisition in the female genital tract.
  
  
  OBJECTIVE
  HIV infection in women is poorly understood. High levels of the hormone progesterone may make women more vulnerable to infection. This could be the case during the menstrual cycle, when using hormone-based birth control, or during pregnancy. The biological basis for increased HIV vulnerability is not known. We used an animal model with high risk for infection during periods of high progesterone. Genital secretions and tissues during the menstrual cycle were studied. Our goal was to identify biological factors upregulated at high progesterone levels, and we indeed show an upregulation of genes and proteins which enhance the ability of HIV to infect when progesterone is high. In contrast, during low-progesterone periods, we found more HIV inhibitory factors. This study contributes to our understanding of mechanisms that may regulate HIV infection in females under hormonal influences. Such knowledge is needed for the development of novel prevention strategies.
authors.affiliation: Division of HIV/AIDS Prevention, CDC, Atlanta, Georgia, USA ile0@cdc.gov.
authors.forename: S A
authors.initials: SA
authors.lastname: Vishwanathan
authors.affiliation: Department of Medical Microbiology and Immunology, University of Manitoba, Winnipeg, Manitoba, Canada National Laboratory for HIV Immunology, JC Wilt Infectious Disease Research Centre, Winnipeg, Manitoba, Canada Unit of Infectious Diseases, Department of Medicine Solna, Center for Molecular Medicine, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.
authors.forename: A
authors.initials: A
authors.lastname: Burgener
authors.affiliation: Nonhuman Primate Genomics Core Laboratory, Yerkes National Primate Research Center, Emory University, Atlanta, Georgia, USA Division of Microbiology & Immunology, Yerkes National Primate Research Center, Emory University, Atlanta, Georgia, USA.
authors.forename: S E
authors.initials: SE
authors.lastname: Bosinger
authors.affiliation: Yerkes National Primate Research Center, Emory University, Atlanta, Georgia, USA.
authors.forename: G K
authors.initials: GK
authors.lastname: Tharp
authors.affiliation: Division of HIV/AIDS Prevention, CDC, Atlanta, Georgia, USA.
authors.forename: P C
authors.initials: PC
authors.lastname: Guenthner
authors.affiliation: Yerkes National Primate Research Center, Emory University, Atlanta, Georgia, USA.
authors.forename: N B
authors.initials: NB
authors.lastname: Patel
authors.affiliation: Department of Medical Microbiology and Immunology, University of Manitoba, Winnipeg, Manitoba, Canada.
authors.forename: K
authors.initials: K
authors.lastname: Birse
authors.affiliation: Division of HIV/AIDS Prevention, CDC, Atlanta, Georgia, USA.
authors.forename: D L
authors.initials: DL
authors.lastname: Hanson
authors.affiliation: National Microbiology Laboratory, Public Health Agency of Canada, Winnipeg, Manitoba, Canada.
authors.forename: G R
authors.initials: GR
authors.lastname: Westmacott
authors.affiliation: Division of HIV/AIDS Prevention, CDC, Atlanta, Georgia, USA.
authors.forename: T R
authors.initials: TR
authors.lastname: Henning
authors.affiliation: Division of HIV/AIDS Prevention, CDC, Atlanta, Georgia, USA.
authors.forename: J
authors.initials: J
authors.lastname: Radzio
authors.affiliation: Division of HIV/AIDS Prevention, CDC, Atlanta, Georgia, USA.
authors.forename: J G
authors.initials: JG
authors.lastname: Garcia-Lerma
authors.affiliation: Department of Medical Microbiology and Immunology, University of Manitoba, Winnipeg, Manitoba, Canada National Laboratory for HIV Immunology, JC Wilt Infectious Disease Research Centre, Winnipeg, Manitoba, Canada.
authors.forename: T B
authors.initials: TB
authors.lastname: Ball
authors.affiliation: Division of HIV/AIDS Prevention, CDC, Atlanta, Georgia, USA.
authors.forename: J M
authors.initials: JM
authors.lastname: McNicholl
authors.affiliation: Division of HIV/AIDS Prevention, CDC, Atlanta, Georgia, USA.
authors.forename: E N
authors.initials: EN
authors.lastname: Kersh
mesh_terms: D000818:Animals; D000998:Antiviral Agents / Q000276:immunology*; D004198:Disease Susceptibility / Q000276:immunology; D030762:Estrous Cycle; D005260:Female; D015658:HIV Infections / Q000276:immunology* / Q000635:transmission; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D007113:Immunity, Innate; D008254:Macaca nemestrina; D012307:Risk Factors; D049490:Systems Biology; D014621:Vagina / Q000276:immunology*
chemical_list: D000998:Antiviral Agents