A SARS-CoV-2-Related Virus from Malayan Pangolin Causes Lung Infection without Severe Disease in Human ACE2-Transgenic Mice.

Coronavirus disease 2019 (COVID-19), which is caused by the novel coronavirus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is the most severe emerging infectious disease in the current century. The discovery of SARS-CoV-2-related coronaviruses (SARSr-CoV-2) in bats and pangolins in South Asian countries indicates that SARS-CoV-2 likely originated from wildlife. To date, two SARSr-CoV-2 strains have been isolated from pangolins seized in Guangxi and Guangdong by the customs agency of China, respectively. However, it remains unclear whether these viruses cause disease in animal models and whether they pose a transmission risk to humans. In this study, we investigated the biological features of a SARSr-CoV-2 strain isolated from a smuggled Malayan pangolin (Manis javanica) captured by the Guangxi customs agency, termed MpCoV-GX, in terms of receptor usage, cell tropism, and pathogenicity in wild-type BALB/c mice, human angiotensin-converting enzyme 2 (ACE2)-transgenic mice, and human ACE2 knock-in mice. We found that MpCoV-GX can utilize ACE2 from humans, pangolins, civets, bats, pigs, and mice for cell entry and infect cell lines derived from humans, monkeys, bats, minks, and pigs. The virus could infect three mouse models but showed limited pathogenicity, with mild peribronchial and perivascular inflammatory cell infiltration observed in lungs. Our results suggest that this SARSr-CoV-2 virus from pangolins has the potential for interspecies infection, but its pathogenicity is mild in mice. Future surveillance among these wildlife hosts of SARSr-CoV-2 is needed to monitor variants that may have higher pathogenicity and higher spillover risk. IMPORTANCE SARS-CoV-2, which likely spilled over from wildlife, is the third highly pathogenic human coronavirus. Being highly transmissible, it is perpetuating a pandemic and continuously posing a severe threat to global public health. Several SARS-CoV-2-related coronaviruses (SARSr-CoV-2) in bats and pangolins have been identified since the SARS-CoV-2 outbreak. It is therefore important to assess their potential of crossing species barriers for better understanding of their risk of future emergence. In this work, we investigated the biological features and pathogenicity of a SARSr-CoV-2 strain isolated from a smuggled Malayan pangolin, named MpCoV-GX. We found that MpCoV-GX can utilize ACE2 from 7 species for cell entry and infect cell lines derived from a variety of mammalian species. MpCoV-GX can infect mice expressing human ACE2 without causing severe disease. These findings suggest the potential of cross-species transmission of MpCoV-GX, and highlight the need of further surveillance of SARSr-CoV-2 in pangolins and other potential animal hosts.

Virome in healthy pangolins reveals compatibility with multiple potentially zoonotic viruses.

Previous studies have identified multiple viruses in dead or severely diseased pangolins, but descriptions of the virome in healthy pangolins are lacking. This poses a greater risk of cross-species transmission due to poor preventive awareness and frequent interactions with breeders. In this study, we investigated the viral composition of 34 pangolins with no signs of disease at the time of sampling and characterized a large number of arthropod-associated viruses belonging to 11 families and vertebrate viruses belonging to eight families, including those with pathogenic potential in humans and animals. Several important vertebrate viruses were identified in the pangolins, including parvovirus, pestivirus, and picobirnavirus. The picobirnavirus was clustered with human and grey teal picobirnaviruses. Viruses with cross-species transmission ability were also identified, including circovirus, rotavirus, and astrovirus. Our study revealed that pangolins are frequently exposed to arthropod-associated viruses in the wild and can carry many vertebrate viruses under natural conditions. This study provides important insights into the virome of pangolins, underscoring the importance of monitoring potential pathogens in healthy pangolins to prevent outbreaks of infectious diseases in domesticated animals and humans.

Differentiation of lipid-poor adenoma from pheochromocytoma on biphasic contrast-enhanced CT.

PURPOSE: To evaluate the diagnostic performance of biphasic contrast-enhanced CT in differentiation of lipid-poor adenomas from pheochromocytomas. METHODS: 129 patients with 132 lipid-poor adenomas and 93 patients with 97 pheochromocytomas confirmed by pathology were included in this retrospective study. Patients underwent unenhanced abdominal CT scan followed by arterial and venous phase. Quantitative and qualitative imaging features were compared between the two groups using univariate analysis. Risk factors for pheochromocytomas were evaluated by multivariate logistic regression analysis and a diagnostic scoring model was established based on odd ratio (OR) of the risk factors. RESULTS: Pheochromocytomas were larger and showed cystic degeneration more frequently compared with lipid-poor adenomas (p < 0.01). No significant difference was found in peak enhancement phase between the two groups (p = 0.348). Attenuation values on unenhanced phase (CTU), arterial phase (CTA), and venous phase (CTV) of pheochromocytomas were significantly higher than that of lipid-poor adenomas while enhancement ratio on arterial and venous phase (ERA, ERV) of pheochromocytomas was significantly lower than that of lipid-poor adenomas (all p < 0.05). Multivariate analysis revealed lesion size > 29 mm (OR: 5.74; 95% CI 2.51-13.16; p < 0.001), CTA > 81 HU (OR: 2.54; 95% CI 1.04-6.17; p = 0.04), CTV > 97 HU (OR: 11.19; 95% CI 3.21-38.97; p < 0.001), ERV ≤ 1.5 (OR: 20.23; 95% CI 6.30-64.87; p < 0.001), and the presence of cystic degeneration (OR: 6.22, 95% CI 1.74-22.25; p = 0.005) were risk factors for pheochromocytomas. The diagnostic scoring model yielded an area under the curve (AUC) of 0.911. CONCLUSIONS: Biphasic contrast-enhanced CT showed good diagnostic performance in differentiation of lipid-poor adenomas from pheochromocytomas.