Reconsidering the Primary Barriers to Coronavirus Emergence
The emergence of coronaviruses (CoVs) has traditionally been attributed to a gain in receptor binding in a new host. Menachery et al. (e01774-19) rescued replication of two Middle East respiratory syndrome CoV (MERS-CoV)-like bat viruses by adding exogenous trypsin. Their results argue that proteolytic cleavage of the spike, not receptor binding, is the primary replication barrier for these group 2C CoVs. Most zoonotic virus sequences are isolated from guano, suggesting an enteric replication cycle in bats. Thus, the presence of exogenous proteases may be required for replication of bat viruses and a key barrier to emergence in a new host.
Absence of compatible host proteases restricts bat CoV infection.
Susceptibility to Mousepox Induced by Chronic Lymphocytic Choriomeningitis Virus Infection Is Rescued by Immunization with Highly Attenuated Ectromelia Virus
C57BL/6 (B6) mice mount natural killer (NK) and T cell responses to wild-type (WT) ectromelia virus (ECTV) and survive without major signs of mousepox. Alves-Peixoto et al. (e01831-19 and e01832-19) found that mice chronically infected with lymphocytic choriomeningitis virus clone 13 (CL13) have defective immune responses to ECTV and succumb to mousepox. When CL13-infected mice were infected with ECTV-Δ036, an attenuated mutant, they survived a subsequent challenge with WT ECTV. This suggests that susceptibility to disease in chronically infected individuals may arise from NK and T cell defects that could be overcome by highly attenuated T cell vaccination.
B6 mice chronically infected with CL13 succumb to mousepox caused by WT ECTV but survive if they were previously immunized with highly attenuated ECTV-Δ036.
Influenza B Viruses Exhibit Very Low Diversity in Human Hosts
Influenza B viruses (IBV) evolve more slowly than influenza A viruses (IAV), but the reasons for this difference are not fully understood. Valesano et al. (e01710-19) found that IBV accumulates less genetic diversity during natural infection then IAV. Data from household transmission pairs suggests that like IAV, IBV experiences a narrow transmission bottleneck. These findings are consistent with the lower mutation rate and lower global rate of evolution for IBV.
Nucleotide diversity per sample of influenza A and B viruses.
Mutations in Bat Influenza Viruses That May Affect Host Tropism
The genomic material of two novel subtypes of influenza virus was previously identified in bats. Zhong et al. (e01416-19) discovered that the replication of an artificially generated bat influenza virus in mammalian cells (not derived from bats) resulted in the emergence of mutations in the neuraminidase (NA)-like protein of the bat influenza virus. These mutations increased virus replication and organ tropism in mice and ferrets. However, the mutant viruses did not cause severe disease in the infected animals. These findings increase our understanding of the ability of bat influenza viruses to adapt to mammals other than bats.
Three-dimensional structure of bat influenza virus NA-like protein (PDB ID 4MC7), showing putative catalytic (blue) and calcium ion (red) binding sites and amino acid positions at which mutations emerged during bat virus passages in cultured cells (green).
β-Catenin Is Required for the cGAS/STING Signaling Pathway but Antagonized by Herpes Simplex Virus 1 US3 Protein
Cyclic GMP-AMP synthase (cGAS) is a cytosolic DNA sensor that induces interferon (IFN) antiviral responses. You et al. (e01847-19) found that β-catenin promotes the cGAS/STING-mediated DNA-sensing signaling pathway, and type I IFN production mediated by β-catenin is antagonized by herpes simplex virus 1 (HSV-1) US3 protein via its kinase activity. US3 interacted with β-catenin and hyperphosphorylated it to block nuclear translocation of the protein. Findings in this study further an understanding of the interaction between the host and HSV-1 infection.
Evasion of β-catenin-mediated DNA-sensing signal pathway by HSV-1 US3.