Body of texts
Flying foxes and bats that belong to the Pteropus genus have been
known to be reservoirs for many different viruses, including
orthoreoviruses. Orthoreoviruses belong to the Reoviridae family
and are known for their ability to infect many mammalian species,
including humans. These so-called Pteropine orthoreoviruses
(PRVs) are named after their reservoir’s genus2. The
first PRV isolate was discovered in bats in 1968 and was named the
Nelson Bay virus for the locale (Nelson Bay in Southeastern Australia)
where it was discovered3. Since then, many PRVs have
been discovered in bats and humans in different parts of the world,
except for those in North and South America (Figure 1), and most of the
recent strains of this virus are genetically related to the original
isolate.
Like other reoviruses, the PRV genome consists of 10 double-stranded RNA
segments (S1-S4, M1-M3, and L1-L3). The segmented genomes allow the
virus to evolve as they increase the potential for genome reassortment,
in which the segmented genome from one strain can exchange with the
segmented genome of another, and thus, enhancing the genetic diversity
of the progeny virus. These genomic exchanges can allow the new virus to
select for more efficient mechanisms of viral entry, genome replication,
immune evasion, and/or expansion of the host range for the
infection4. This particular viral lifestyle can
increase inter- and intraspecies transmission events, making these
viruses more adaptable to different host species and more prone to cause
disease outbreaks5-9.
Out of the seventeen (17) currently known PRV strains (Table 1), eight
(8) have been isolated from bats, one (1) has been isolated from
non-human primates and another eight (8) have been isolated from humans
who either live in areas where these PRVs are endemic or from travelers
to endemic areas. Some of the human cases have resulted from either
direct contact with the infected fruit bats or human-to-human
transmission events. PRV often causes flu-like symptoms, and for this
reason, it is either not being diagnosed immediately or is often being
misdiagnosed. Also, most of the currently available clinical respiratory
diagnostic assays do not include PRV as a potential candidate, which can
lead to undiagnosed patients5,6. In severe cases, PRV
infection can lead to acute respiratory distress syndrome, the mechanism
of which is unknown10-12.
A recent article published in the Journal of Medical
Virology 1 looked at the role of PRV as a causative
agent for acute respiratory infections (ARI) in humans. In this article,
the authors selected patients who were being seen at the primary care
clinics in Kuala Lumpur, Malaysia from March 2012 to May 2014 for
ARI-related symptoms. A total of 3,935 nasal swab samples were collected
and tested using the xTAG Respiratory Viral Panel FAST assay, which can
detect fifteen different respiratory viruses. Forty-nine percent (49%)
of those samples were negative for any known respiratory viruses. When
632 of those samples were then tested for PRVs, 14 (2.2%) of them were
positive for these viruses. The authors also reported higher
PRV-positive incidences in their patients in August of 2013 (13.3%) and
April and May of 2014 (20% and 33.3%, respectively). Additionally,
they were able to sequence the new PRV genomic segments that showed a
new reassortant strain (PRV18UM), which consists of the segmented
genomes from both the Melaka and Kampar virus strains. They used this
new strain of the virus to assess its replication kinetics in human
cardiomyocyte cell line (AC16), African green-monkey cell line (Vero),
and human oral keratinocytes and nasopharyngeal epithelial cell lines
(OKF-6 and NP69). Even though this new strain of the virus replicated
slower in the OKF-6 and NP69 cells than in the AC16 and Vero cells, it
was shown for the first time to be able to replicate in human head and
neck cells. Interestingly, the authors also observed that the S segments
from most PRV strains isolated from humans in their cohort were a
mixture of the viral genomic segments from both non-human primate and
bat strains, which strongly suggests this as a mechanism of
cross-species transmissions among three different mammalian species,
among other genetic diversification mechanisms observed.
This editor’s choice article1 reports the first PRV
surveillance effort in urban areas, which suggests that PRVs are more
prevalent in populated areas than have previously been presumed. As PRVs
are zoonotic viruses, people who are living and/or working in densely
populated areas or in congregate settings (e.g., airports, hospitals,
nursing homes, childcare centers, schools, indoor sporting and other
entertainment facilities, restaurants, jails, prisons, shelters,
residential living facilities, etc.) and those who are living in rural
areas and/or are more likely to be exposed to fruit bats need to be more
aware of the potential exposure to these emerging viruses. Public health
officials in endemic regions also need to consider conducting routine
surveillance for these emerging viruses to prevent potential future
disease outbreaks caused by these Pteropine orthoreoviruses
(PRVs).
Disclosure statement: No potential conflict of interest was reported by
the authors.
Funding: The authors reported no funding associated with the work
featured in this article.
Acknowledgments: W.V.R. was supported in part by the NIH T32 AI055433
Infectious Disease Training in Clinical Investigation Program at the
University of Minnesota, Twin Cities
Data availability statement: No primary data are included in this
article.
References:
- Tee KK, Chan PQ, Loh AM, Singh
S, Teo CH, Iyadorai T, Chook JB, Ng KT, Takebe Y, Chan KG, Sam IC,
Voon K. Surveillance, Isolation and Genomic Characterization of
Pteropine orthoreovirus of Probable Bat Origin Among Patients with
Acute Respiratory Infection in Malaysia. J Med Virol. 2023 Jan 24.
doi: 10.1002/jmv.28520. Epub ahead of print. PMID: 36691929.
- Voon, K., Chua, K.B., Yu, M., Crameri, G., Barr, J.A., Malik, Y.,
Wang, L.-F., 2011. Evolutionary relationship of the L- and M-class
genome segments of bat-borne fusogenic orthoreoviruses in Malaysia and
Australia. Journal of General Virology 92, 2930-2936.
- Gard, G.P. and Marshall, I.D., 1973. Nelson Bay virus: a novel
reovirus. Archiv für die gesamte Virusforschung , 43 ,
pp.34-42.
- Chao L, Tran TT, Tran TT. 1997. The advantage of sex in the RNA virus
phi6. Genetics 147:953-9.
- Chua, K.B., Crameri, G., Hyatt, A., Yu, M., Tompang, M.R., Rosli, J.,
McEachern, J., Crameri, S., Kumarasamy, V., Eaton, B.T., Wang, L.F.,
2007. A previously unknown reovirus of bat origin is associated with
an acute respiratory disease in humans. Proceedings of the National
Academy of Sciences 104, 11424-11429.
- Chua, K.B., Voon, K., Crameri, G., Tan, H.S., Rosli, J., McEachern,
J.A., Suluraju, S., Yu, M., Wang, L.-F., 2008. Identification and
Characterization of a New Orthoreovirus from Patients with Acute
Respiratory Infections. PLoS ONE 3, e3803.
- Singh, H., Shimojima, M., Ngoc, T.C., Quoc Huy, N.V., Chuong, T.X., Le
Van, A., Saijo, M.,Yang, M., Sugamata, M., 2015. Serological evidence
of human infection with Pteropine orthoreovirus in Central Vietnam.
Journal of Medical Virology 87, 2145-2148.
- Uehara, A., Tan, C.W., Mani, S., Chua, K.B., Leo, Y.S., Anderson,
D.E., Wang, L.F., 2019. Serological evidence of human infection by bat
orthoreovirus in Singapore. Journal of Medical Virology 91, 707-710.
- Leong, W.J., Quek, X.F., Tan, H.Y., Wong, K.M., Muhammad, H.S.,
Mohamed, N.A., Wong, S.T., Abdullah, M.L., Leong, P.P., Wang, L.,
Voon, K., 2022. Seroprevalence of Pteropine orthoreovirus in humans
remain similar after nearly two decades (2001-2002 vs. 2017) in Tioman
Island, Malaysia. Journal of Medical Virology 94, 771-775.
- Cheng, P., Lau, C.S., Lai, A., Ho, E., Leung, P., Chan, F., Wong, A.,
Lim, W., 2009. A novel reovirus isolated from a patient with acute
respiratory disease. Journal of Clinical Virology 45, 79-80.
- Wong, A.H., Cheng, P.K.C., Lai, M.Y.Y., Leung, P.C.K., Wong, K.K.Y.,
Lee, W.Y., Lim, W.W.L., 2012. Virulence Potential of Fusogenic
Orthoreoviruses. Emerging Infectious Diseases 18.
- Yamanaka, A., Iwakiri, A., Yoshikawa, T., Sakai, K., Singh, H.,
Himeji, D., Kikuchi, I., Ueda, A., Yamamoto, S., Miura, M., Shioyama,
Y., Kawano, K., Nagaishi, T., Saito, M., Minomo, M., Iwamoto, N.,
Hidaka, Y., Sohma, H., Kobayashi, T., Kanai, Y., Kawagishi, T.,
Nagata, N., Fukushi, S., Mizutani, T., Tani, H., Taniguchi, S.,
Fukuma, A., Shimojima, M., Kurane, I., Kageyama, T., Odagiri, T.,
Saijo, M., Morikawa, S., 2014. Imported Case of Acute Respiratory
Tract Infection Associated with a Member of Species Nelson Bay
Orthoreovirus. PLoS ONE 9, e92777.