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Association of chronic wasting disease susceptibility with prion protein variation in white-tailed deer (Odocoileus virginianus).

ABSTRACT: Chronic wasting disease (CWD) is caused by prions, infectious proteinaceous particles, PrP^CWD. We sequenced the PRNP gene of 2,899 white-tailed deer (WTD) from Illinois and southern Wisconsin, finding 38 haplotypes. Haplotypes A, B, D, E, G and 9 others encoded Q₉₅G₉₆S₁₀₀N₁₀₃A₁₂₃Q₂₂₆, designated 'PrP variant A.' Haplotype C and 4 other haplotypes encoded PrP 'variant C' (Q₉₅S₉₆S₁₀₀N₁₀₃A₁₂₃Q₂₂₆). Haplotype F and two other haplotypes encoded PrP 'variant F' (H₉₅G₉₆S₁₀₀N₁₀₃A₁₂₃Q₂₂₆). The association of CWD with encoded PrP variants was examined in 2,537 tested WTD from counties with CWD. Relative to PrP variant A, CWD susceptibility was lower in deer with PrP variant C (OR = 0.26, p < 0.001), and even lower in deer with PrP variant F (OR = 0.10, p < 0.0001). Susceptibility to CWD was highest in deer with both chromosomes encoding PrP variant A, lower with one copy encoding PrP variant A (OR = 0.25, p < 0.0001) and lowest in deer without PrP variant A (OR = 0.07, p < 0.0001). There appeared to be incomplete dominance for haplotypes encoding PrP variant C in reducing CWD susceptibility. Deer with both chromosomes encoding PrP variant F (FF) or one encoding PrP variant C and the other F (CF) were all CWD negative. Our results suggest that an increased population frequency of PrP variants C or F and a reduced frequency of PrP variant A may reduce the risk of CWD infection. Understanding the population and geographic distribution of PRNP polymorphisms may be a useful tool in CWD management.

SUBMITTER: Ishida Y

PROVIDER: S-EPMC7518741 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:The origin of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus causing the global coronavirus disease 19 (COVID-19) pandemic, remains a mystery. Current evidence suggests a likely spillover into humans from an animal reservoir. Understanding the host range and identifying animal species that are susceptible to SARS-CoV-2 infection may help to elucidate the origin of the virus and the mechanisms underlying cross-species transmission to humans. Here we demonstrated that white-tailed deer (Odocoileus virginianus), an animal species in which the angiotensin converting enzyme 2 (ACE2) - the SARS-CoV-2 receptor - shares a high degree of similarity to humans, are highly susceptible to infection. Intranasal inoculation of deer fawns with SARS-CoV-2 resulted in established subclinical viral infection and shedding of infectious virus in nasal secretions. Notably, infected animals transmitted the virus to non-inoculated contact deer. Viral RNA was detected in multiple tissues 21 days post-inoculation (pi). All inoculated and indirect contact animals seroconverted and developed neutralizing antibodies as early as day 7 pi. The work provides important insights into the animal host range of SARS-CoV-2 and identifies white-tailed deer as a susceptible wild animal species to the virus.IMPORTANCEGiven the presumed zoonotic origin of SARS-CoV-2, the human-animal-environment interface of COVID-19 pandemic is an area of great scientific and public- and animal-health interest. Identification of animal species that are susceptible to infection by SARS-CoV-2 may help to elucidate the potential origin of the virus, identify potential reservoirs or intermediate hosts, and define the mechanisms underlying cross-species transmission to humans. Additionally, it may also provide information and help to prevent potential reverse zoonosis that could lead to the establishment of a new wildlife hosts. Our data show that upon intranasal inoculation, white-tailed deer became subclinically infected and shed infectious SARS-CoV-2 in nasal secretions and feces. Importantly, indirect contact animals were infected and shed infectious virus, indicating efficient SARS-CoV-2 transmission from inoculated animals. These findings support the inclusion of wild cervid species in investigations conducted to assess potential reservoirs or sources of SARS-CoV-2 of infection.

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Association of chronic wasting disease susceptibility with prion protein variation in white-tailed deer (Odocoileus virginianus).

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