Ocular tropism of SARS-CoV-2 in animal models with retinal inflammation via neuronal invasion following intranasal inoculation

Gi Uk Jeong; Hyung-Jun Kwon; Wern Hann Ng; Xiang Liu; Hyun Woo Moon; Gun Young Yoon; Hye Jin Shin; In-Chul Lee; Zheng Lung Ling; Alanna G Spiteri; Nicholas J C King; Adam Taylor; Ji Soo Chae; Chonsaeng Kim; Dae-Gyun Ahn; Kyun-Do Kim; Young Bae Ryu; Seong-Jun Kim; Suresh Mahalingam; Young-Chan Kwon

doi:10.1038/s41467-022-35225-1

Ocular tropism of SARS-CoV-2 in animal models with retinal inflammation via neuronal invasion following intranasal inoculation

Nat Commun. 2022 Dec 12;13(1):7675. doi: 10.1038/s41467-022-35225-1.

Authors

Gi Uk Jeong^#¹, Hyung-Jun Kwon^#^{2

3}, Wern Hann Ng^{4

5

6}, Xiang Liu^{4

5

6}, Hyun Woo Moon¹, Gun Young Yoon¹, Hye Jin Shin^{1

7}, In-Chul Lee^{2

3}, Zheng Lung Ling^{8

9}, Alanna G Spiteri^{8

9}, Nicholas J C King^{4

8

9

10

11}, Adam Taylor^{4

5

6}, Ji Soo Chae¹², Chonsaeng Kim¹, Dae-Gyun Ahn¹, Kyun-Do Kim¹, Young Bae Ryu², Seong-Jun Kim¹, Suresh Mahalingam^{4

5

6}, Young-Chan Kwon¹³

Affiliations

¹ Department of Convergent Research of Emerging Virus Infection, Korea Research Institute of Chemical Technology, Daejeon, 34114, Republic of Korea.
² Department of Functional Biomaterial Research Center, Korea Research Institute of Bioscience and Biotechnology, Jeongeup, 56212, Republic of Korea.
³ Center for Companion Animal New Drug Development, Jeonbuk Branch, Korea Institute of Toxicology, Jeongeup, 53212, Republic of Korea.
⁴ Emerging Viruses, Inflammation and Therapeutics Group, Menzies Health Institute Queensland, Griffith University, Gold Coast, QLD, Australia.
⁵ Global Virus Network (GVN) Centre of Excellence in Arboviruses, Griffith University, Gold Coast, QLD, Australia.
⁶ School of Pharmacy and Medical Sciences, Griffith University, Gold Coast, QLD, Australia.
⁷ Department of Microbiology, Chungnam National University School of Medicine, Daejeon, 35015, Republic of Korea.
⁸ Viral Immunopathology Laboratory, The Charles Perkins Centre, The University of Sydney, Sydney, NSW, 2006, Australia.
⁹ School of Medical Sciences, Faculty of Medicine and Health, The University of Sydney, Sydney, NSW, 2006, Australia.
¹⁰ Sydney Institute for Infectious Diseases, The University of Sydney, Sydney, NSW, 2006, Australia.
¹¹ Sydney Nano, The University of Sydney, Sydney, NSW, 2006, Australia.
¹² Department of Life Sciences, PerkinElmer, Seoul, 08380, Republic of Korea.
¹³ Department of Convergent Research of Emerging Virus Infection, Korea Research Institute of Chemical Technology, Daejeon, 34114, Republic of Korea. [email protected].

^# Contributed equally.

Abstract

Although ocular manifestations are reported in patients with COVID-19, consensus on ocular tropism of SARS-CoV-2 is lacking. Here, we infect K18-hACE2 transgenic mice with SARS-CoV-2 using various routes. We observe ocular manifestation and retinal inflammation with production of pro-inflammatory cytokines in the eyes of intranasally (IN)-infected mice. Intratracheal (IT) infection results in dissemination of the virus from the lungs to the brain and eyes via trigeminal and optic nerves. Ocular and neuronal invasions are confirmed using intracerebral (IC) infection. Notably, the eye-dropped (ED) virus does not cause lung infection and becomes undetectable with time. Ocular and neurotropic distribution of the virus in vivo is evident in fluorescence imaging with an infectious clone of SARS-CoV-2-mCherry. The ocular tropic and neuroinvasive characteristics of SARS-CoV-2 are confirmed in wild-type Syrian hamsters. Our data can improve the understanding regarding viral transmission and clinical characteristics of SARS-CoV-2 and help in improving COVID-19 control procedures.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
COVID-19*
Cricetinae
Disease Models, Animal
Inflammation
Lung
Mesocricetus
Mice
Mice, Transgenic
SARS-CoV-2*