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. 2018 Dec 19;10(12):727.
doi: 10.3390/v10120727.

SARS-Like Coronavirus WIV1-CoV Does Not Replicate in Egyptian Fruit Bats (Rousettus aegyptiacus)

Neeltje van Doremalen  1 , Alexandra Schäfer  2 , Vineet D Menachery  3 , Michael Letko  4 , Trenton Bushmaker  5 , Robert J Fischer  6 , Dania M Figueroa  7 , Patrick W Hanley  8 , Greg Saturday  9 , Ralph S Baric  10 , Vincent J Munster  11
Affiliations

SARS-Like Coronavirus WIV1-CoV Does Not Replicate in Egyptian Fruit Bats (Rousettus aegyptiacus)

Neeltje van Doremalen et al. Viruses. .

Abstract

Severe acute respiratory syndrome (SARS)-like WIV1-coronavirus (CoV) was first isolated from Rhinolophus sinicus bats and can use the human angiotensin converting enzyme 2 (ACE2) receptor. In the current study, we investigate the ability of WIV1-CoV to infect Rousettus aegyptiacus bats. No clinical signs were observed throughout the experiment. Furthermore, only four oropharyngeal swabs and two respiratory tissues, isolated on day 3 post inoculation, were found positive for viral RNA. Two out of twelve bats showed a modest increase in coronavirus specific antibodies post challenge. In conclusion, WIV1-CoV was unable to cause a robust infection in Rousettus aegyptiacus bats.

Keywords: WIV1-CoV; animal model; coronavirus; emerging infectious diseases.

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Conflict of interest statement

The authors declare no conflicts of interest.

Figures

Figure 1
Figure 1
Egyptian fruit bat ACE2 is a suitable receptor for WIV1-CoV. (A) Schematic overview of coronavirus spike proteins. (B) VSV particles pseudotyped with coronavirus spike proteins were concentrated and analyzed for spike incorporation by Western blot. (C) BHK cells were transfected with coronavirus receptors and infected with pseudotyped particles in triplicate. (D) BHK cells were transfected with ACE2 plasmids and inoculated with WIV1-CoV at a MOI of 0.01, 24 h after transfection. Supernatants were harvested at 0, and 48 hpi and viral titers were determined by endpoint titration in quadruplicate in VeroE6 cells.
Figure 2
Figure 2
ACE2 immunohistochemistry of (A) nasal turbinate—400×, multifocal apical immunoreactivity in ciliated epithelial cells (arrows); (B) trachea—400×, negative immunostaining; (C) lung—400×, multifocal cytoplasmic endothelial cell immunoreactivity (arrowheads): (D) kidney—200×, multifocal cytoplasmic endothelial cell immunoreactivity (arrowheads); (E) stomach—400×, multifocal cytoplasmic endothelial cell immunoreactivity (arrowheads): (F) intestine—100×, diffuse immunoreactivity of brush border.
Figure 3
Figure 3
Disease symptoms, shedding and tissue tropism after inoculation with WIV1-CoV. (A) Relative weight change and (B) body temperature change in Egyptian fruit bats following inoculation with WIV1-CoV. (C) Viral RNA in oropharyngeal, rectal, and urogenital swabs obtained daily. (D) Lung:body weight ratio of Egyptian fruit bats at 3, 7, and 28 dpi. (E) Viral RNA load in tissues obtained 3 dpi (N = 4 bats).
Figure 4
Figure 4
Hematology of Egyptian fruit bats inoculated with WIV1-CoV. Pre-challenge values (black) were obtained at D-95 (N = 12) and D-2 (N = 11). Post-challenge values were obtained at 3 dpi (red), 7 dpi (blue), and 28 dpi (green). All values were measured using the IDEXX ProCyte DX Analyzer. Dotted line = average of pre-challenge values.
Figure 5
Figure 5
Serology titers in sera obtained pre- and post-challenge. ELISA assays were performed using SARS-CoV proteins N and S. Bats with an increase in serology titer are shown in bold.
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