Epidemiological studies have revealed the emergence of multiple SARS-CoV-2 variants of concern (VOC), including the lineage B.1.1.7 that is rapidly replacing old variants. The B.1.1.7 variant has been linked to increased morbidity rates, transmissibility, and potentially mortality. To assess viral fitness in vivo and to address whether the B.1.1.7 variant is capable of immune escape, we conducted infection and re-infection studies in naive and convalescent Syrian hamsters (>10 months old). Hamsters infected by either a B.1.1.7 variant or a B.1 (G614) variant exhibited comparable viral loads and pathology. Convalescent hamsters that were previously infected by the original D614 variant were protected from disease following B.1.1.7 challenge with no observable clinical signs or lung pathology. Altogether, our study did not find that the B.1.1.7 variant significantly differs from the B.1 variant in pathogenicity in hamsters and that natural infection-induced immunity confers protection against a secondary challenge by the B1.1.7 variant.
The sequence of Zika virus has evolved as it has spread out of Africa and into the Americas. It is unclear whether American strains of the virus define a new serotype. Here, we have tested the virulence and immunogenicity of three wild-type ZIKV strains in neonatal Swiss Webster mice. We found that all three ZIKV strains (African MR766, 1947; Asian FSS13025, 2010; and American, PRVABC59, 2015) are capable of killing neonatal mice after intracranial injection. Intraperitoneal injection with these viruses did not kill, but produced neutralizing antibodies as measured by a PRNT 50 assay. Sera from mice infected with each virus were tested for neutralizing activity against the infecting virus and also the other two viruses by a PRNT 50 assay. In general, the antibodies induced by each virus were good at neutralizing that virus (the homologous virus), but somewhat poorer at neutralizing the other two viruses (heterologous viruses). Antibodies induced by the African strain MR766 were about 4-fold worse at neutralizing the American strain PRVABC59 than the homologous strain, while antibodies induced by the American strain were about 10-fold worse at neutralizing the African strain than the homologous strain. Because the antibodies are cross-neutralizing at some level, the viruses do not form separate serotypes. Nevertheless, these results raise concern that the immunity conferred by the African virus may protect only relatively poorly against the new American strains. This has implications for the possible spread of the American ZIKV strains to Africa and Southeast Asia, and also for the development of vaccines.
18Members of Flavivirus, a genus of Flaviviridae, encompass numerous enveloped plus strand 19 RNA viruses, of which globally dengue virus (DENV) is the leading cause of serious arthropod-20 borne disease. The genomes of DENV, just as those of yellow fever virus (YFV), West Nile 21 2 fever virus (WNV), or Zika virus (ZIKV), control their translation by a 5'-terminal capping 22 group. Three other genera of Flaviviridae are remarkable because their viruses use internal 23 ribosomal entry sites (IRESs) to control translation and they are not arthropod transmitted. In 24 2006 E. Harris' group published work suggesting that DENV RNA does not stringently need a 25 109 virus at the end point of experiments roughly equal to that of the transcripts with the functional 110 m 7 G cap (Fig. 1). As we have observed previously (8), infectious virus yields were always 111 6slightly higher in C6/36 cells than in BHK cells. This observation suggests that DENV infection 112 is more productive in mosquito cells compared to mammalian cells. 113Both the m 7 GpppA-capped and unmethylated GpppA-capped DENV transcripts produced 114 similar viral titers on BHK cells post transfection (Fig. 1). Therefore, we carried out a detailed 115 assay of infectivity with the two uncapped pppAN-and GpppAN-DENV genome transcripts 116 wondering if we would find major differences in specific infectivity of the in vitro RNAs. 117Samples were harvested daily (up to day 5) from medium and used for focus forming assays in 118 Vero cells (see Materials and Methods). The result showed that the pppA-DENV2 genome RNA 119 produced viral titers that were 2-3 log10 lower than those obtained with the unmethylated 120 GpppA-5'modified RNAs (Fig. S1). This observation is in accordance with a previous report 121 obtained with transcripts of yellow fever virus cDNA (11). We assume that the viruses harvested 122 at the end of the incubation contain genomes with DENV-specific capping groups. The reason is 123 that the viral replication machinery, that was newly assembled in the course of the replication 124 cycle, will provide newly synthesized genomes with the 5' terminal modification (12)(13)(14). 125Experiments to test this hypothesis are currently in progress. 126As was mentioned in the Introduction, there are different possibilities to explain the infectivity of 127 uncapped DENV transcripts (see Discussion). In the following we report our experiments to test 128 the DENV and ZIKV 5' UTRs for IRES competence. 129 Translation of mono-cistronic mRNAs under the control of DENV 5'-UTR variants in 130 mammalian cells 131To test whether the uncapped transcripts of the DENV cDNA harbor an activity that allows cap-132 independent translation we designed mono-cistronic mRNAs 5' terminated with either pppAN, 133 GpppAN or m 7 GpppAN, followed by the 96-nt-long DENV 5'-UTR sequence (D5; Fig. 2) and 134 7 the Gluc ORF (15). We chose two different 3' termini, the DENV 3'-UTR (D3) because of its 135 possible role in DENV translation (16) or the polyadenylated 3'-UTR (P) of poli...
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