Serological evidence and experimental infection of cynomolgus macaques with pteropine orthoreovirus reveal monkeys as potential hosts for transmission to humans

Abstract

Pteropine orthoreoviruses (PRV) are emerging bat-borne viruses with proven zoonotic transmission. We recently demonstrated human exposure to PRV in Singapore, which together with previous reports from Malaysia and Vietnam suggest that human infection of PRV may occur periodically in the region. This raises the question whether bats are the only sources of human infection. In this study, we screened 517 cynomolgus macaques caught in Singapore for evidence of exposure to PRV3M (also known as Melaka virus), which was first isolated from human patients in Melaka, Malaysia. We found that 67 serum samples were PRV3M positive by ELISA and 34 were also positive by virus neutralization assay. To investigate whether monkeys could act as hosts for PRV transmission, we experimentally infected cynomolgus macaques with PRV3M and housed these animals with uninfected monkeys. Although no clinical signs of infection were observed in infected animals, viral RNA was detected in nasal and rectal swabs and all infected macaques seroconverted. Additionally, one of the uninfected animals seroconverted, implying active shedding and transmission of PRV3M. We provide evidence that PRV exposure in the macaque population in Singapore occurs at a relatively high prevalence and this study suggests that cynomolgus macaques may be an intermediate or reservoir host for PRVs.

Pteropine Orthoreovirus in an Angolan Soft-Furred Fruit Bat (Lissonycteris angolensis) in Uganda Dramatically Expands the Global Distribution of an Emerging Bat-Borne Respiratory Virus

“…This provides evidence that S2 and S4 diversity, across the geographic distribution of PRV, is not significantly structured by factors such as host species. In other words, PRV appears to have a broad host tropism [3]. We note that our analyses assume that human PRV infections were acquired locally, or, for imported cases, at the reported site of infection.…”

“…Although the mechanism by which PRV transmits between bat species across the range of the virus remains incompletely known, these studies suggested that co-roosting behavior is a major driver of such transmission. The transmission of PRV between related bat species should occur with relative ease under permissive ecological conditions, given the aforementioned zoonotic potential of PRV and further evidence of infection of wild crab-eating macaques (Macaca fascicularis) in Singapore [3] and Thailand [45]. We anticipate that future surveys of pteropids bats of south Asia, the Middle East, and the Horn of Africa may further expand the range of PRV and fill the gaps in the geographic continuum of genetic distance that we have documented.…”

“…Pteropine orthoreovirus (PRV; Reoviridae: Spinareovirinae) is a bat-borne zoonosis that causes upper respiratory tract infection (URTI), ranging from mild respiratory symptoms to influenza-like illness (ILI), in Southeast Asia [1][2][3][4]. PRV is a fusogenic orthoreovirus with 10 dsRNA segments (S1-4, M1-3, L1-3) [5].…”

Host BAG3 Is Degraded by Pseudorabies Virus pUL56 C-Terminal 181L-185L and Plays a Negative Regulation Role during Viral Lytic Infection

“…In the performed infection assays, HEK293T cells were employed to investigate the effects of BAG3 overexpression or knockdown on lytic infection of PRV. We used HEK293T cells because: (i) Human cell lines are susceptible to PRV, and support the efficient replication of PRV [35,36], (ii) HEK293T cells are highly efficient for overexpression of foreign protein by the transfected plasmid, and (iii) PRV has been reported in several recent case reports to infect humans, which results in encephalitis [37][38][39][40][41][42]. Both overexpression and knockdown assays indicated that BAG3 played a negative regulation role during PRV lytic infection.…”

Distinct interferon response in bat and other mammalian cell lines infected with Pteropine orthoreovirus

“…Bats are well recognized as natural hosts of multiple highly pathogenic zoonotic viruses, such as Marburg virus [ 1 ], SARS-CoV [ 2 ], MERS-CoV [ 3 ], Hendra virus [ 4 ], Nipah virus [ 5 ], and Ebola virus [ 6 ]. Viral transmission to humans directly from bats or via other animals as intermediate hosts has occurred previously, causing fatal outbreaks in humans and suggesting an important role of bats in disease transmission [ 1 , 7 – 9 ].…”