Zika virus (ZIKV) is a mosquito-transmitted flavivirus that since 2013 has exploded into a pandemic causing severe disease across the South Pacific and the Western Hemisphere. Even from the first large outbreak in 2007 on Yap Island, epidemiological data suggested that the virus may have unusual transmission characteristics and disease bias among age and sex strata of humans. The majority of people affected with disease on Yap were females and age groups over 30, despite homogenous exposure as measured by antibodies. In 2011, the PI published the first evidence suggesting that Zika virus could be transmitted directly through sexual intercourse. The subsequent pandemic has produced confirmatory evidence of this novel observation, including isolations of ZIKV from human urine and semen and at least 2 other cases of sexual transmission. These data highlight the urogenital tropism of ZIKV, which undoubtedly affects its transmission dynamics, and subsequently the epidemiology of ZIKV disease and pathology. We will test the hypothesis that ZIKV has a strong tropism to certain tissues in the mammalian urogenital tract, such as the prostate gland in males, and is excreted in the bodily fluids of infected animals, and that this fosters sexual transmission and differential pathology in between sexes.
The first aim i s understand the frequency and details of urogenital tropism and shedding of ZIKV from humans displaying symptoms of arboviral disease who are enrolled into a small human cohort study at the center of the pandemic in northeastern Brazil.
The second aim i s to develop an animal model of Zika virus urogenital infection, pathogenesis and sexual transmission.

Public Health Relevance

This project aims to understand how Zika virus localizes to the urogenital tract and is shed in the bodily fluids of infected individuals. Urogenital localization and shedding is expected to facilitate sexual transmission of this virus. Studies will be with people infected with Zika virus in northeastern Brazil, and with animal models.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Exploratory/Developmental Grants (R21)
Project #
5R21AI129464-02
Application #
9397518
Study Section
Special Emphasis Panel (ZAI1)
Program Officer
Challberg, Mark D
Project Start
2016-12-15
Project End
2018-11-30
Budget Start
2017-12-01
Budget End
2018-11-30
Support Year
2
Fiscal Year
2018
Total Cost
Indirect Cost
Name
Colorado State University-Fort Collins
Department
Microbiology/Immun/Virology
Type
Schools of Veterinary Medicine
DUNS #
785979618
City
Fort Collins
State
CO
Country
United States
Zip Code
80523
Magalhaes, Tereza; Foy, Brian D; Marques, Ernesto T A et al. (2017) Mosquito-borne and sexual transmission of Zika virus: Recent developments and future directions. Virus Res :
Chotiwan, Nunya; Brewster, Connie D; Magalhaes, Tereza et al. (2017) Rapid and specific detection of Asian- and African-lineage Zika viruses. Sci Transl Med 9: