{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T14:01:06Z","timestamp":1790776866677,"version":"4.1.0"},"reference-count":58,"publisher":"American Society for Microbiology","issue":"7","license":[{"start":{"date-parts":[[2026,7,8]],"date-time":"2026-07-08T00:00:00Z","timestamp":1783468800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,7,8]],"date-time":"2026-07-08T00:00:00Z","timestamp":1783468800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"DOI":"10.13039\/501100001407","name":"Department of Biotechnology, Ministry of Science and Technology, India","doi-asserted-by":"publisher","award":["BT\/PR50989\/COT\/142\/52\/2023"],"award-info":[{"award-number":["BT\/PR50989\/COT\/142\/52\/2023"]}],"id":[{"id":"10.13039\/501100001407","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100011753","name":"National Institute of Immunology","doi-asserted-by":"publisher","award":["NII-Core"],"award-info":[{"award-number":["NII-Core"]}],"id":[{"id":"10.13039\/501100011753","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R35GM148351"],"award-info":[{"award-number":["R35GM148351"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["mBio"],"published-print":{"date-parts":[[2026,7,8]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title\/>\n                    <jats:p>\n                      Viruses transit from a low to high multiplicity of infection (MOI) regime in infected tissues. Type-1 interferons (IFNs) enforce a cellular state refractory to virus multiplication, while the death of infected cells eliminates viral replicative niche. Here, we investigated how these two innate antiviral mechanisms cooperate at various MOIs upon cell infection by Chandipura virus (CHPV), a cytopathic RNA virus implicated in several outbreaks of acute encephalitis in India. We found that as expected, a gradual increase in the input MOI from 0.02 to 2 led to a proportionate surge in the viral yield. Surprisingly, a further rise to MOI 20 caused a reduction in the progeny titer. Our mathematical modeling together with\n                      <jats:italic toggle=\"yes\">ex vivo<\/jats:italic>\n                      infection studies involving knockout cells suggested that cell death\u2014more so than virus-induced type-1 IFNs\u2014restricted CHPV propagation at cell-saturating high MOIs, leading to a net fall in the yield at MOI 20. We argue that the distinct involvement of innate immune pathways at varied MOIs imparts robust cellular defense against cytopathic viruses.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>IMPORTANCE<\/jats:title>\n                    <jats:p>After host invasion, a limited number of viruses initially provide for a low multiplicity of infection (MOI) of tissue cells. Ongoing viral multiplication allows for high multiplicity infection of host cells at a later stage. Type-1 IFNs and cell death constitute two principal arms of the antiviral cellular defense. We probed infection of cultured cells by Chandipura virus (CHPV), a virus implicated in encephalitis outbreaks, at various MOI. We find that CHPV propagation is restricted mainly through type-1 IFNs at low MOI and cell death at high MOI. Cell death not only destroys the viral replicative niche but also orchestrates pathological inflammation. In fact, moderating inflammation represents an important objective in the symptomatic management of viral diseases. While the proposed model needs to be tested for other viruses, our findings may bear significance for therapeutic intervention strategies and timing in viral diseases.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1128\/mbio.01013-26","type":"journal-article","created":{"date-parts":[[2026,6,15]],"date-time":"2026-06-15T13:03:01Z","timestamp":1781528581000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":1,"title":["A dominant role of cell death in limiting Chandipura virus propagation at cell-saturating high multiplicity of infection"],"prefix":"10.1128","volume":"17","author":[{"family":"Bhawna","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/04fhee747","id-type":"ROR","asserted-by":"publisher"}],"name":"Systems Immunology Laboratory, National Institute of Immunology","place":["New Delhi, 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