Immune System Modulation and Viral Persistence in Bats: Understanding Viral Spillover
<p>Evolution of tolerance to DNA damage and unique antiviral immune response in bats. Development of flight necessitated the evolution of bats with the ability to modulate the consequences of increased metabolic activity by suppressing inflammation (left). Inflammation was suppressed by dampening the activation of DNA sensors, such as STING, and reducing levels of inflammatory cytokines, such as TNFα (center). These traits were positively selected but a reduced inflammatory response made it advantageous for virus replication (lower right). Increased susceptibility of cells to virus replication was compensated by selection of more effective antiviral measures, such as higher constitutive expression of Interferons or unique ISG expressions (upper right). (Abbreviations used: cGAS—cyclic GMP-AMP synthase, GTP—Guanosine triphosphate, cGMP—cyclic guanosine monophosphate, STING—stimulator of interferon genes, TBK1—TANK binding kinase 1, IRF3—interferon regulatory transcription factor 3, cRel, TNFα—tumor necrosis factor α, RNase-L—ribonuclease L).</p> "> Figure 2
<p>Model showing effect of stress on persistent viral infection. Viruses persistently infect bats due to their reduced inflammation (reduced DNA sensor activation and decreased inflammatory cytokine levels) and their effective antiviral immune response (increased constitutive expression of interferons and unique ISG expressions), as depicted in <a href="#viruses-11-00192-f001" class="html-fig">Figure 1</a>. Stressful events alter the balance between host and virus and lead to an increase in virus replication, thereby leading to viral shedding.</p> ">
Abstract
:1. Introduction
2. Bats Have an Efficient and Varied Antiviral Response
3. Bats Suppress the Pathological Effects of Excessive Virus-Induced Inflammation
Unique Immune Features and Relationship with the Evolution of Flight
4. Viral Persistence in Bats
5. Stress-Induced Spillover—A Molecular Perspective
6. Future Directions
Funding
Conflicts of Interest
References
- Hayman, D.T.S. Bats as Viral Reservoirs. Annu. Rev. Virol. 2016, 3, 77–99. [Google Scholar] [CrossRef] [PubMed]
- Luby, S.; Rahman, M.; Hossain, M.; Blum, L.; Husain, M.; Gurley, E.; Khan, R.; Ahmed, B.-N.; Rahman, S.; Nahar, N.; et al. Foodborne Transmission of Nipah Virus, Bangladesh. Emerg. Infect. Dis. 2006, 12, 1888–1894. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Edson, D.; Field, H.; McMichael, L.; Vidgen, M.; Goldspink, L.; Broos, A.; Melville, D.; Kristoffersen, J.; de Jong, C.; McLaughlin, A.; et al. Routes of Hendra Virus Excretion in Naturally-Infected Flying-Foxes: Implications for Viral Transmission and Spillover Risk. PLoS ONE 2015, 10, e0140670. [Google Scholar] [CrossRef] [PubMed]
- Field, H.; Young, P.; Yob, J.M.; Mills, J.; Hall, L.; Mackenzie, J. The natural history of Hendra and Nipah viruses. Microbes Infect. 2001, 3, 307–314. [Google Scholar] [CrossRef]
- Kurup, A. From bats to pigs to man: The story of Nipah Virus. Infect. Dis. Clin. Pract. 2002, 11, 52–57. [Google Scholar] [CrossRef]
- Islam, M.S.; Sazzad, H.M.S.; Satter, S.M.; Sultana, S.; Hossain, M.J.; Hasan, M.; Rahman, M.; Campbell, S.; Cannon, D.L.; Ströher, U.; et al. Nipah Virus Transmission from Bats to Humans Associated with Drinking Traditional Liquor Made from Date Palm Sap, Bangladesh, 2011–2014. Emerg. Infect. Dis. 2016, 22, 664–670. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Vogel, G. Bat-filled tree source of Ebola epidemic? Science 2015, 347, 142–143. [Google Scholar] [CrossRef] [Green Version]
- Caron, A.; Bourgarel, M.; Cappelle, J.; Liégeois, F.; De Nys, H.M.; Roger, F. Ebola Virus Maintenance: If Not (Only) Bats, What Else? Viruses 2018, 10, 549. [Google Scholar] [CrossRef] [PubMed]
- Goldstein, T.; Anthony, S.J.; Gbakima, A.; Bird, B.H.; Bangura, J.; Tremeau-Bravard, A.; Belaganahalli, M.N.; Wells, H.L.; Dhanota, J.K.; Liang, E.; et al. The discovery of Bombali virus adds further support for bats as hosts of ebolaviruses. Nat. Microbiol. 2018, 3, 1084–1089. [Google Scholar] [CrossRef] [PubMed]
- Yang, X.-L.; Tan, C.W.; Anderson, D.E.; Jiang, R.-D.; Li, B.; Zhang, W.; Zhu, Y.; Lim, X.F.; Zhou, P.; Liu, X.-L.; et al. Characterization of a filovirus (Měnglà virus) from Rousettus bats in China. Nat. Microbiol. 2019, 4, 390–395. [Google Scholar] [CrossRef] [PubMed]
- Streicker, D.G.; Turmelle, A.S.; Vonhof, M.J.; Kuzmin, I.V.; McCracken, G.F.; Rupprecht, C.E. Host Phylogeny Constrains Cross-Species Emergence and Establishment of Rabies Virus in Bats. Science 2010, 329, 676–679. [Google Scholar] [CrossRef] [PubMed]
- Plowright, R.K.; Eby, P.; Hudson, P.J.; Smith, I.L.; Westcott, D.; Bryden, W.L.; Middleton, D.; Reid, P.A.; McFarlane, R.A.; Martin, G.; et al. Ecological dynamics of emerging bat virus spillover. Proc. Biol. Sci. R. Soc. 2015, 282, 20142124. [Google Scholar] [CrossRef] [PubMed]
- Duggal, N.K.; Emerman, M. Evolutionary conflicts between viruses and restriction factors shape immunity. Nat. Rev. Immunol. 2012, 12, 687–695. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Baker, M.L.; Schountz, T.; Wang, L.F. Antiviral immune responses of bats: A review. Zoonoses Public Health 2013, 60, 104–116. [Google Scholar] [CrossRef] [PubMed]
- Schountz, T. Immunology of Bats and Their Viruses: Challenges and Opportunities. Viruses 2014, 6, 4880–4901. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Schountz, T.; Baker, M.L.; Butler, J.; Munster, V. Immunological Control of Viral Infections in Bats and the Emergence of Viruses Highly Pathogenic to Humans. Front. Immunol. 2017, 8, 1098. [Google Scholar] [CrossRef] [PubMed]
- Peixoto, F.P.; Braga, P.H.P.; Mendes, P. A synthesis of ecological and evolutionary determinants of bat diversity across spatial scales. BMC Ecol. 2018, 18, 18. [Google Scholar] [CrossRef] [PubMed]
- Zhou, P.; Tachedjian, M.; Wynne, J.W.; Boyd, V.; Cui, J.; Smith, I.; Cowled, C.; Ng, J.H.J.; Mok, L.; Michalski, W.P.; et al. Contraction of the type I IFN locus and unusual constitutive expression of IFN-α in bats. Proc. Natl. Acad. Sci. USA 2016, 113, 2696–2701. [Google Scholar] [CrossRef] [PubMed]
- O’Connor, K.C. Bats are “blind” to the deadly effects of viruses. Sci. Immunol. 2018, 3, eaau2559. [Google Scholar] [CrossRef] [PubMed]
- O’Shea, T.J.; Cryan, P.M.; Cunningham, A.A.; Fooks, A.R.; Hayman, D.T.; Luis, A.D.; Peel, A.J.; Plowright, R.K.; Wood, J.L. Bat flight and zoonotic viruses. Emerg. Infect. Dis. 2014, 20, 741–745. [Google Scholar] [CrossRef] [PubMed]
- Zhang, G.; Cowled, C.; Shi, Z.; Huang, Z.; Bishop-Lilly, K.A.; Fang, X.; Wynne, J.W.; Xiong, Z.; Baker, M.L.; Zhao, W.; et al. Comparative analysis of bat genomes provides insight into the evolution of flight and immunity. Science 2013, 339, 456–460. [Google Scholar] [CrossRef] [PubMed]
- Omatsu, T.; Bak, E.-J.; Ishii, Y.; Kyuwa, S.; Tohya, Y.; Akashi, H.; Yoshikawa, Y. Induction and sequencing of Rousette bat interferon alpha and beta genes. Vet. Immunol. Immunopathol. 2008, 124, 169–176. [Google Scholar] [CrossRef] [PubMed]
- Zhou, P.; Cowled, C.; Todd, S.; Crameri, G.; Virtue, E.R.; Marsh, G.A.; Klein, R.; Shi, Z.; Wang, L.-F.; Baker, M.L. Type III IFNs in Pteropid Bats: Differential Expression Patterns Provide Evidence for Distinct Roles in Antiviral Immunity. J. Immunol. 2011, 186, 3138–3147. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Pavlovich, S.S.; Lovett, S.P.; Koroleva, G.; Guito, J.C.; Arnold, C.E.; Nagle, E.R.; Kulcsar, K.; Lee, A.; Thibaud-Nissen, F.; Hume, A.J.; et al. The Egyptian Rousette Genome Reveals Unexpected Features of Bat Antiviral Immunity. Cell 2018, 173, 1098–1110. [Google Scholar] [CrossRef] [PubMed]
- De La Cruz-Rivera, P.C.; Kanchwala, M.; Liang, H.; Kumar, A.; Wang, L.-F.; Xing, C.; Schoggins, J.W. The IFN Response in Bats Displays Distinctive IFN-Stimulated Gene Expression Kinetics with Atypical RNASEL Induction. J. Immunol. 2018, 200, 209–217. [Google Scholar] [CrossRef] [PubMed]
- Li, Y.; Banerjee, S.; Wang, Y.; Goldstein, S.A.; Dong, B.; Gaughan, C.; Silverman, R.H.; Weiss, S.R. Activation of RNase L is dependent on OAS3 expression during infection with diverse human viruses. Proc. Natl. Acad. Sci. USA 2016, 113, 2241–2246. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Gerrard, D.L.; Hawkinson, A.; Sherman, T.; Modahl, C.M.; Hume, G.; Campbell, C.L.; Schountz, T.; Frietze, S. Transcriptomic Signatures of Tacaribe Virus-Infected Jamaican Fruit Bats. mSphere 2017, 2, e00245-17. [Google Scholar] [CrossRef] [PubMed]
- Channappanavar, R.; Perlman, S. Pathogenic human coronavirus infections: Causes and consequences of cytokine storm and immunopathology. Semin. Immunopathol. 2017, 39, 529–539. [Google Scholar] [CrossRef] [PubMed]
- Banerjee, A.; Rapin, N.; Bollinger, T.; Misra, V. Lack of inflammatory gene expression in bats: A unique role for a transcription repressor. Sci. Rep. 2017, 7, 2232. [Google Scholar] [CrossRef] [PubMed]
- Xie, J.; Li, Y.; Shen, X.; Goh, G.; Zhu, Y.; Cui, J.; Wang, L.-F.; Shi, Z.-L.; Zhou, P. Dampened STING-Dependent Interferon Activation in Bats. Cell Host Microbe 2018, 23, 297–301. [Google Scholar] [CrossRef] [PubMed]
- Ahn, M.; Cui, J.; Irving, A.T.; Wang, L.-F. Unique Loss of the PYHIN Gene Family in Bats amongst Mammals: Implications for Inflammasome Sensing. Sci. Rep. 2016, 6, 21722. [Google Scholar] [CrossRef] [PubMed]
- Maina, J.N. What it takes to fly: The structural and functional respiratory refinements in birds and bats. J. Exp. Biol. 2000, 203, 3045–3064. [Google Scholar] [PubMed]
- Thomas, S.P.; Suthers, R.A. The Physiology and Energetics of Bat Flight. J. Exp. Biol. 1972, 57, 317–335. [Google Scholar]
- Cadet, J.; Wagner, J.R. DNA Base Damage by Reactive Oxygen Species, Oxidizing Agents, and UV Radiation. Cold Spring Harb. Perspect. Biol. 2013, 5, a012559. [Google Scholar] [CrossRef] [PubMed]
- Sheldon, B.C.; Verhulst, S. Ecological immunology: Costly parasite defences and trade-offs in evolutionary ecology. Trends Ecol. Evol. 1996, 11, 317–321. [Google Scholar] [CrossRef]
- Jebb, D.; Foley, N.M.; Whelan, C.V.; Touzalin, F.; Puechmaille, S.J.; Teeling, E.C. Population level mitogenomics of long-lived bats reveals dynamic heteroplasmy and challenges the Free Radical Theory of Ageing. Sci. Rep. 2018, 8, 13634. [Google Scholar] [CrossRef] [PubMed]
- Cogswell-Hawkinson, A.; Bowen, R.; James, S.; Gardiner, D.; Calisher, C.H.; Adams, R.; Schountz, T. Tacaribe virus causes fatal infection of an ostensible reservoir host, the Jamaican fruit bat. J. Virol. 2012, 86, 5791–5799. [Google Scholar] [CrossRef] [PubMed]
- Middleton, D.J.; Morrissy, C.J.; van der Heide, B.M.; Russell, G.M.; Braun, M.A.; Westbury, H.A.; Halpin, K.; Daniels, P.W. Experimental Nipah virus infection in pteropid bats (Pteropus poliocephalus). J. Comp. Pathol. 2007, 136, 266–272. [Google Scholar] [CrossRef] [PubMed]
- Munster, V.J.; Adney, D.R.; van Doremalen, N.; Brown, V.R.; Miazgowicz, K.L.; Milne-Price, S.; Bushmaker, T.; Rosenke, R.; Scott, D.; Hawkinson, A.; et al. Replication and shedding of MERS-CoV in Jamaican fruit bats (Artibeus jamaicensis). Sci. Rep. 2016, 6, 21878. [Google Scholar] [CrossRef] [PubMed]
- Jones, M.E.B.; Schuh, A.J.; Amman, B.R.; Sealy, T.K.; Zaki, S.R.; Nichol, S.T.; Towner, J.S. Experimental Inoculation of Egyptian Rousette Bats (Rousettus aegyptiacus) with Viruses of the Ebolavirus and Marburgvirus Genera. Viruses 2015, 7, 3420–3442. [Google Scholar] [CrossRef] [PubMed]
- Sohayati, A.R.; Hassan, L.; Sharifah, S.H.; Lazarus, K.; Zaini, C.M.; Epstein, J.H.; Naim, N.S.; Field, H.E.; Arshad, S.S.; Aziz, J.A.; et al. Evidence for Nipah virus recrudescence and serological patterns of captive Pteropus vampyrus. Epidemiol. Infect. 2011, 139, 1570–1579. [Google Scholar] [CrossRef] [PubMed]
- Amman, B.R.; Jones, M.E.; Sealy, T.K.; Uebelhoer, L.S.; Schuh, A.J.; Bird, B.H.; Coleman-McCray, J.D.; Martin, B.E.; Nichol, S.T.; Towner, J.S. Oral shedding of marburg virus in experimentally infected Egyptian fruit bats (Rousettus aegyptiacus). J. Wildl. Dis. 2015, 51, 113–124. [Google Scholar] [CrossRef] [PubMed]
- Schuh, A.J.; Amman, B.R.; Jones, M.E.B.; Sealy, T.K.; Uebelhoer, L.S.; Spengler, J.R.; Martin, B.E.; Coleman-McCray, J.A.D.; Nichol, S.T.; Towner, J.S. Modelling filovirus maintenance in nature by experimental transmission of Marburg virus between Egyptian rousette bats. Nat. Commun. 2017, 8, 14446. [Google Scholar] [CrossRef] [PubMed]
- Subudhi, S.; Rapin, N.; Bollinger, T.K.; Hill, J.E.; Donaldson, M.E.; Davy, C.M.; Warnecke, L.; Turner, J.M.; Kyle, C.J.; Willis, C.K.R.; et al. A persistently infecting coronavirus in hibernating Myotis lucifugus, the North American little brown bat. J. Gen. Virol. 2017, 98, 2297–2309. [Google Scholar] [CrossRef] [PubMed]
- Peel, A.J.; Baker, K.S.; Hayman, D.T.S.; Broder, C.C.; Cunningham, A.A.; Fooks, A.R.; Garnier, R.; Wood, J.L.N.; Restif, O. Support for viral persistence in bats from age-specific serology and models of maternal immunity. Sci. Rep. 2018, 8, 3859. [Google Scholar] [CrossRef] [PubMed]
- Halpin, K.; Hyatt, A.D.; Fogarty, R.; Middleton, D.; Bingham, J.; Epstein, J.H.; Rahman, S.A.; Hughes, T.; Smith, C.; Field, H.E.; et al. Pteropid bats are confirmed as the reservoir hosts of henipaviruses: A comprehensive experimental study of virus transmission. Am. J. Trop. Med. Hyg. 2011, 85, 946–951. [Google Scholar] [CrossRef] [PubMed]
- Plowright, R.K.; Peel, A.J.; Streicker, D.G.; Gilbert, A.T.; McCallum, H.; Wood, J.; Baker, M.L.; Restif, O. Transmission or Within-Host Dynamics Driving Pulses of Zoonotic Viruses in Reservoir–Host Populations. PLoS Negl. Trop. Dis. 2016, 10, e0004796. [Google Scholar] [CrossRef] [PubMed]
- Prösch, S.; Wendt, C.E.C.; Reinke, P.; Priemer, C.; Oppert, M.; Krüger, D.H.; Volk, H.-D.; Döcke, W.-D. A Novel Link between Stress and Human Cytomegalovirus (HCMV) Infection: Sympathetic Hyperactivity Stimulates HCMV Activation. Virology 2000, 272, 357–365. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Grinde, B. Herpesviruses: Latency and reactivation—Viral strategies and host response. J. Oral Microbiol. 2013, 5. [Google Scholar] [CrossRef] [PubMed]
- Knickelbein, J.E.; Khanna, K.M.; Yee, M.B.; Baty, C.J.; Kinchington, P.R.; Hendricks, R.L. Noncytotoxic lytic granule-mediated CD8+ T cell inhibition of HSV-1 reactivation from neuronal latency. Science 2008, 322, 268–271. [Google Scholar] [CrossRef] [PubMed]
- Freeman, M.L.; Sheridan, B.S.; Bonneau, R.H.; Hendricks, R.L. Psychological Stress Compromises CD8+ T Cell Control of Latent Herpes Simplex Virus Type 1 Infections. J. Immunol. 2007, 179, 322–328. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Flaño, E.; Kim, I.J.; Woodland, D.L.; Blackman, M.A. Gamma-herpesvirus latency is preferentially maintained in splenic germinal center and memory B cells. J. Exp. Med. 2002, 196, 1363–1372. [Google Scholar] [CrossRef] [PubMed]
- Weck, K.E.; Barkon, M.L.; Yoo, L.I.; Speck, S.H.; Virgin Hw, I.V. Mature B cells are required for acute splenic infection, but not for establishment of latency, by murine gammaherpesvirus 68. J. Virol. 1996, 70, 6775–6780. [Google Scholar] [PubMed]
- Lieberman, P.M. Keeping it quiet: Chromatin control of gammaherpesvirus latency. Nat. Rev. Microbiol. 2013, 11, 863–875. [Google Scholar] [CrossRef] [PubMed]
- Lee, M.; Choi, I.; Park, K. Activation of stress signaling molecules in bat brain during arousal from hibernation. J. Neurochem. 2002, 82, 867–873. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Subudhi, S.; Rapin, N.; Dorville, N.; Hill, J.E.; Town, J.; Willis, C.K.R.; Bollinger, T.K.; Misra, V. Isolation, characterization and prevalence of a novel Gammaherpesvirus in Eptesicus fuscus, the North American big brown bat. Virology 2018, 516, 227–238. [Google Scholar] [CrossRef] [PubMed]
- Gerow, C.M.; Rapin, N.; Voordouw, M.J.; Elliot, M.; Misra, V.; Subudhi, S. Arousal from hibernation and reactivation of Eptesicus fuscus gammaherpesvirus (Ef HV) in big brown bats. Transbound. Emerg. Dis. 2018. [Google Scholar] [CrossRef] [PubMed]
- Liberto, M.C.; Zicca, E.; Pavia, G.; Quirino, A.; Marascio, N.; Torti, C.; Focà, A. Virological Mechanisms in the Coinfection between HIV and HCV. Mediat. Inflamm. 2015, 2015, 320532. [Google Scholar] [CrossRef] [PubMed]
- Verant, M.L.; Meteyer, C.U.; Speakman, J.R.; Cryan, P.M.; Lorch, J.M.; Blehert, D.S. White-nose syndrome initiates a cascade of physiologic disturbances in the hibernating bat host. BMC Physiol. 2014, 14, 10. [Google Scholar] [CrossRef] [PubMed]
- Warnecke, L.; Turner, J.M.; Bollinger, T.K.; Misra, V.; Cryan, P.M.; Blehert, D.S.; Wibbelt, G.; Willis, C.K. Pathophysiology of white-nose syndrome in bats: A mechanistic model linking wing damage to mortality. Biol. Lett. 2013, 9, 20130177. [Google Scholar] [CrossRef] [PubMed]
- McGuire, L.P.; Mayberry, H.W.; Willis, C.K.R. White-nose syndrome increases torpid metabolic rate and evaporative water loss in hibernating bats. Am. J. Physiol. Regul. Integr. Comp. Physiol. 2017, 313, R680–R686. [Google Scholar] [CrossRef] [PubMed]
- Davy, C.M.; Donaldson, M.E.; Subudhi, S.; Rapin, N.; Warnecke, L.; Turner, J.M.; Bollinger, T.K.; Kyle, C.J.; Dorville, N.A.S.; Kunkel, E.L.; et al. White-nose syndrome is associated with increased replication of a naturally persisting coronaviruses in bats. Sci. Rep. 2018, 8, 15508. [Google Scholar] [CrossRef] [PubMed]
- Olival, K.J.; Hosseini, P.R.; Zambrana-Torrelio, C.; Ross, N.; Bogich, T.L.; Daszak, P. Host and viral traits predict zoonotic spillover from mammals. Nature 2017, 546, 646–650. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Kumar, N.; Kulkarni, D.D.; Lee, B.; Kaushik, R.; Bhatia, S.; Sood, R.; Pateriya, A.K.; Bhat, S.; Singh, V.P. Evolution of Codon Usage Bias in Henipaviruses Is Governed by Natural Selection and Is Host-Specific. Viruses 2018, 10, 604. [Google Scholar] [CrossRef] [PubMed]
- Behura, S.K.; Severson, D.W. Codon usage bias: Causative factors, quantification methods and genome-wide patterns: With emphasis on insect genomes. Biol. Rev. Camb. Philos. Soc. 2013, 88, 49–61. [Google Scholar] [CrossRef] [PubMed]
- Lau, S.K.P.; Zhang, L.; Luk, H.K.H.; Xiong, L.; Peng, X.; Li, K.S.M.; He, X.; Zhao, P.S.-H.; Fan, R.Y.Y.; Wong, A.C.P.; et al. Receptor Usage of a Novel Bat Lineage C Betacoronavirus Reveals Evolution of Middle East Respiratory Syndrome-Related Coronavirus Spike Proteins for Human Dipeptidyl Peptidase 4 Binding. J. Infect. Dis. 2018, 218, 197–207. [Google Scholar] [CrossRef] [PubMed]
- Yang, Y.; Du, L.; Liu, C.; Wang, L.; Ma, C.; Tang, J.; Baric, R.S.; Jiang, S.; Li, F. Receptor usage and cell entry of bat coronavirus HKU4 provide insight into bat-to-human transmission of MERS coronavirus. Proc. Natl. Acad. Sci. USA 2014, 111, 12516–12521. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Huang, C.; Qi, J.; Lu, G.; Wang, Q.; Yuan, Y.; Wu, Y.; Zhang, Y.; Yan, J.; Gao, G.F. Putative Receptor Binding Domain of Bat-Derived Coronavirus HKU9 Spike Protein: Evolution of Betacoronavirus Receptor Binding Motifs. Biochemistry 2016, 55, 5977–5988. [Google Scholar] [CrossRef] [PubMed]
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Subudhi, S.; Rapin, N.; Misra, V. Immune System Modulation and Viral Persistence in Bats: Understanding Viral Spillover. Viruses 2019, 11, 192. https://doi.org/10.3390/v11020192
Subudhi S, Rapin N, Misra V. Immune System Modulation and Viral Persistence in Bats: Understanding Viral Spillover. Viruses. 2019; 11(2):192. https://doi.org/10.3390/v11020192
Chicago/Turabian StyleSubudhi, Sonu, Noreen Rapin, and Vikram Misra. 2019. "Immune System Modulation and Viral Persistence in Bats: Understanding Viral Spillover" Viruses 11, no. 2: 192. https://doi.org/10.3390/v11020192