Open AccessModeling mosquito-borne and sexual transmission of Zika virus in an enzootic host, the African green monkey
Author(s) -
Andrew D. Haddow,
Unai Pérez-Sautu,
Michael R. Wiley,
Lynn J. Miller,
Adrienne E. Kimmel,
Lucia M. Principe,
Suzanne Wollen-Roberts,
Joshua D. Shamblin,
Stephanie M. Valdez,
Lisa H. Cazares,
William D. Pratt,
Franco Rossi,
Luis A. LugoRoman,
Sina Bavari,
Gustavo Palacios,
Aysegul Nalca,
Farooq Nasar,
M. Louise M. Pitt
Publication year - 2020
Publication title -
plos neglected tropical diseases
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.99
H-Index - 135
eISSN - 1935-2735
pISSN - 1935-2727
DOI - 10.1371/journal.pntd.0008107
Subject(s) - viremia , virology , zika virus , virus , infectious dose , biology , viral shedding , sexual transmission , transmission (telecommunications) , vero cell , neutralizing antibody , titer , medicine , microbicide , human immunodeficiency virus (hiv) , electrical engineering , engineering
Mosquito-borne and sexual transmission of Zika virus (ZIKV), a TORCH pathogen, recently initiated a series of large epidemics throughout the Tropics. Animal models are necessary to determine transmission risk and study pathogenesis, as well screen antivirals and vaccine candidates. In this study, we modeled mosquito and sexual transmission of ZIKV in the African green monkey (AGM). Following subcutaneous, intravaginal or intrarectal inoculation of AGMs with ZIKV, we determined the transmission potential and infection dynamics of the virus. AGMs inoculated by all three transmission routes exhibited viremia and viral shedding followed by strong virus neutralizing antibody responses, in the absence of clinical illness. All four of the subcutaneously inoculated AGMs became infected (mean peak viremia: 2.9 log 10 PFU/mL, mean duration: 4.3 days) and vRNA was detected in their oral swabs, with infectious virus being detected in a subset of these specimens. Although all four of the intravaginally inoculated AGMs developed virus neutralizing antibody responses, only three had detectable viremia (mean peak viremia: 4.0 log 10 PFU/mL, mean duration: 3.0 days). These three AGMs also had vRNA and infectious virus detected in both oral and vaginal swabs. Two of the four intrarectally inoculated AGMs became infected (mean peak viremia: 3.8 log 10 PFU/mL, mean duration: 3.5 days). vRNA was detected in oral swabs collected from both of these infected AGMs, and infectious virus was detected in an oral swab from one of these AGMs. Notably, vRNA and infectious virus were detected in vaginal swabs collected from the infected female AGM (peak viral load: 7.5 log 10 copies/mL, peak titer: 3.8 log 10 PFU/mL, range of detection: 5–21 days post infection). Abnormal clinical chemistry and hematology results were detected and acute lymphadenopathy was observed in some AGMs. Infection dynamics in all three AGM ZIKV models are similar to those reported in the majority of human ZIKV infections. Our results indicate that the AGM can be used as a surrogate to model mosquito or sexual ZIKV transmission and infection. Furthermore, our results suggest that AGMs are likely involved in the enzootic maintenance and amplification cycle of ZIKV.