Attenuation of replication by a 29 nucleotide deletion in SARS-coronavirus acquired during the early stages of human-to-human transmission.

Muth, DoreenDoreenMuthCorman, Victor MaxVictor MaxCormanRoth, HannaHannaRothBinger, TabeaTabeaBingerDijkman, RonaldRonaldDijkmanGottula, Lina TheresaLina TheresaGottulaGloza-Rausch, FlorianFlorianGloza-RauschBalboni, AndreaAndreaBalboniBattilani, MaraMaraBattilaniRihtarič, DanijelaDanijelaRihtaričToplak, IvanIvanToplakAmeneiros, Ramón SeageRamón SeageAmeneirosPfeifer, AlexanderAlexanderPfeiferThiel, Volker EarlVolker EarlThielDrexler, Jan FelixJan FelixDrexlerMüller, Marcel AlexanderMarcel AlexanderMüllerDrosten, ChristianChristianDrosten2025-01-082025-01-082018-10-11https://boris-portal.unibe.ch/handle/20.500.12422/200459A 29 nucleotide deletion in open reading frame 8 (ORF8) is the most obvious genetic change in severe acute respiratory syndrome coronavirus (SARS-CoV) during its emergence in humans. In spite of intense study, it remains unclear whether the deletion actually reflects adaptation to humans. Here we engineered full, partially deleted (-29 nt), and fully deleted ORF8 into a SARS-CoV infectious cDNA clone, strain Frankfurt-1. Replication of the resulting viruses was compared in primate cell cultures as well as Rhinolophus bat cells made permissive for SARS-CoV replication by lentiviral transduction of the human angiotensin-converting enzyme 2 receptor. Cells from cotton rat, goat, and sheep provided control scenarios that represent host systems in which SARS-CoV is neither endemic nor epidemic. Independent of the cell system, the truncation of ORF8 (29 nt deletion) decreased replication up to 23-fold. The effect was independent of the type I interferon response. The 29 nt deletion in SARS-CoV is a deleterious mutation acquired along the initial human-to-human transmission chain. The resulting loss of fitness may be due to a founder effect, which has rarely been documented in processes of viral emergence. These results have important implications for the retrospective assessment of the threat posed by SARS.en600 - Technology::630 - Agriculture500 - Science::570 - Life sciences; biology600 - Technology::610 - Medicine & healthAttenuation of replication by a 29 nucleotide deletion in SARS-coronavirus acquired during the early stages of human-to-human transmission.article10.7892/boris.1275203031010410.1038/s41598-018-33487-8