ZIKV Demonstrates Minimal Pathologic Effects and Mosquito Infectivity in Viremic Cynomolgus Macaques

Sasha R Azar; Shannan L Rossi; Sherry H Haller; Ruimei Yun; Jing H Huang; Jessica A Plante; Jiehua Zhou; Juan P Olano; Christopher M Roundy; Kathryn A Hanley; Scott C Weaver; Nikos Vasilakis

doi:10.3390/v10110661

ZIKV Demonstrates Minimal Pathologic Effects and Mosquito Infectivity in Viremic Cynomolgus Macaques

Viruses. 2018 Nov 21;10(11):661. doi: 10.3390/v10110661.

Authors

Sasha R Azar^{1

2

3}, Shannan L Rossi^{4

5

6

7}, Sherry H Haller⁸, Ruimei Yun⁹, Jing H Huang¹⁰, Jessica A Plante¹¹, Jiehua Zhou¹², Juan P Olano¹³, Christopher M Roundy^{14

15}, Kathryn A Hanley¹⁶, Scott C Weaver^{17

18

19

20

21}, Nikos Vasilakis^{22

23

24}

Affiliations

¹ Department of Pathology, University of Texas Medical Branch, Galveston, TX 77555, USA. srazar@utmb.edu.
² Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX 77555, USA. srazar@utmb.edu.
³ Institute for Translational Sciences, University of Texas Medical Branch, Galveston, TX 77555, USA. srazar@utmb.edu.
⁴ Department of Pathology, University of Texas Medical Branch, Galveston, TX 77555, USA. slrossi@utmb.edu.
⁵ Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX 77555, USA. slrossi@utmb.edu.
⁶ Institute for Human Infections and Immunity, University of Texas Medical Branch, Galveston, TX 77555, USA. slrossi@utmb.edu.
⁷ World Reference Center for Emerging Viruses and Arboviruses, University of Texas Medical Branch, Galveston, TX 77555, USA. slrossi@utmb.edu.
⁸ Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX 77555, USA. shhaller@utmb.edu.
⁹ Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX 77555, USA. ruyun@utmb.edu.
¹⁰ Department of Pathology, University of Texas Medical Branch, Galveston, TX 77555, USA. jinghong2018@yahoo.com.
¹¹ Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX 77555, USA. japlante@utmb.edu.
¹² Department of Pathology, University of Texas Medical Branch, Galveston, TX 77555, USA. jiehzhou@utmb.edu.
¹³ Department of Pathology, University of Texas Medical Branch, Galveston, TX 77555, USA. jolano@utmb.edu.
¹⁴ Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX 77555, USA. cmroundy@utmb.edu.
¹⁵ Institute for Translational Sciences, University of Texas Medical Branch, Galveston, TX 77555, USA. cmroundy@utmb.edu.
¹⁶ Department of Biology, New Mexico State University, Las Cruces, NM 88003, USA. khanley@nmsu.edu.
¹⁷ Department of Pathology, University of Texas Medical Branch, Galveston, TX 77555, USA. sweaver@utmb.edu.
¹⁸ Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX 77555, USA. sweaver@utmb.edu.
¹⁹ Institute for Translational Sciences, University of Texas Medical Branch, Galveston, TX 77555, USA. sweaver@utmb.edu.
²⁰ Institute for Human Infections and Immunity, University of Texas Medical Branch, Galveston, TX 77555, USA. sweaver@utmb.edu.
²¹ World Reference Center for Emerging Viruses and Arboviruses, University of Texas Medical Branch, Galveston, TX 77555, USA. sweaver@utmb.edu.
²² Department of Pathology, University of Texas Medical Branch, Galveston, TX 77555, USA. nivasila@utmb.edu.
²³ Institute for Human Infections and Immunity, University of Texas Medical Branch, Galveston, TX 77555, USA. nivasila@utmb.edu.
²⁴ World Reference Center for Emerging Viruses and Arboviruses, University of Texas Medical Branch, Galveston, TX 77555, USA. nivasila@utmb.edu.

Abstract

To evaluate the effects of ZIKV infection on non-human primates (NHPs), as well as to investigate whether these NHPs develop sufficient viremia to infect the major urban vector mosquito, Aedes aegypti, four cynomolgus macaques (Macaca fascicularis) were subcutaneously infected with 5.0 log₁₀ focus-forming units (FFU) of DNA clone-derived ZIKV strain FSS13025 (Asian lineage, Cambodia, 2010). Following infection, the animals were sampled (blood, urine, tears, and saliva), underwent daily health monitoring, and were exposed to Ae. aegypti at specified time points. All four animals developed viremia, which peaked 3⁻4 days post-infection at a maximum value of 6.9 log₁₀ genome copies/mL. No virus was detected in urine, tears, or saliva. Infection by ZIKV caused minimal overt disease: serum biochemistry and CBC values largely fell within the normal ranges, and cytokine elevations were minimal. Strikingly, the minimally colonized population of Ae. aegypti exposed to viremic animals demonstrated a maximum infection rate of 26% during peak viremia, with two of the four macaques failing to infect a single mosquito at any time point. These data indicate that cynomolgus macaques may be an effective model for ZIKV infection of humans and highlights the relative refractoriness of Ae. aegypti for ZIKV infection at the levels of viremia observed.

Keywords: Aedes aegypti; Flaviviridae; Macaca fascicularis; Zika virus; pathogenesis; vector competence.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Aedes / virology*
Animals
Blood / virology
Disease Models, Animal
Disease Transmission, Infectious*
Macaca fascicularis*
Mosquito Vectors / virology*
Saliva / virology
Tears / virology
Urine / virology
Viral Load
Viremia
Zika Virus Infection / pathology*
Zika Virus Infection / transmission
Zika Virus Infection / virology*

Abstract

Publication types

MeSH terms

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