Susceptibility of tree shrew to SARS-CoV-2 infection

Abstract

Since severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) became a pandemic event in the world, it has not only caused huge economic losses, but also a serious threat to global public health. Many scientific questions about SARS-CoV-2 and Coronavirus disease (COVID-19) were raised and urgently need to be answered, including the susceptibility of animals to SARS-CoV-2 infection. Here we tested whether tree shrew, an emerging experimental animal domesticated from wild animal, is susceptible to SARS-CoV-2 infection. No clinical signs were observed in SARS-CoV-2 inoculated tree shrews during this experiment except the increasing body temperature particularly in female animals. Low levels of virus shedding and replication in tissues occurred in all three age groups. Notably, young tree shrews (6 months to 12 months) showed virus shedding at the earlier stage of infection than adult (2 years to 4 years) and old (5 years to 7 years) animals that had longer duration of virus shedding comparatively. Histopathological examine revealed that pulmonary abnormalities were the main changes but mild although slight lesions were also observed in other tissues. In summary, tree shrew is less susceptible to SARS-CoV-2 infection compared with the reported animal models and may not be a suitable animal for COVID-19 related researches. However, tree shrew may be a potential intermediate host of SARS-CoV-2 as an asymptomatic carrier.

Figure 1

Study design and body temperature in SARS-CoV-2 infected tree shrews. (a) Total 35 tree shrews (Tupaia belangeris) were used for infection in this study. Two challenge experiments were conducted with 1 ml 10⁶ pfu SARS-CoV-2 nasally (500 μl/each). Twenty-four animals for the first experiment were divided into three groups (young, adult and old) according to ages. Each group included half male and half female. Following the viral inoculation, clinical observation and viral load assay were performed as indicated. Animals were dissected in about two weeks post viral inoculation. (b) On every other day as indicated in (a), body temperature of tree shrew was monitored and recorded. The software Graphpad was utilized for data processing and plotting as rainbow heat map. X represents no data collected. Body temperature beyond 39 °C was shown in white boxes.

Figure 2

Histopathological examination in SARS-CoV-2 infected tree shrews. On 4, 7 and 14/16 dpi, tree shrews were euthanized and dissected. Tissues were collected from each animal for H&E staining and histopathological analysis. The histological sites with typical and representative lesions were zoomed in, which was described in text. (a) Histological lesions in the pulmonary tissues. The representative images were shown here from young, adult and old tree shrews dissected at the different stages of SARS-CoV-2 infection. (b) Histopathological changes in the other twelve tissues. Each image here represents one tissue of an animal, including weasand, Hilar, heart, liver, small intestine, pancreas, cecum, rectum, spleen, kidney, uterus, brain. Histopathological score of tissues in all tree shrews was summarized in Table 3.