UK B.1.1.7 variant exhibits increased respiratory replication and shedding in nonhuman primates.

The continuing emergence of SARS-CoV-2 variants calls for regular assessment to identify differences in viral replication, shedding and associated disease. In this study, African green monkeys were infected intranasally with either a contemporary D614G or the UK B.1.1.7 variant. Both variants caused mild respiratory disease with no significant differences in clinical presentation. Significantly higher levels of viral RNA and infectious virus were found in upper and lower respiratory tract samples and tissues from B.1.1.7 infected animals. Interestingly, D614G infected animals showed significantly higher levels of viral RNA and infectious virus in rectal swabs and gastrointestinal tract tissues. Our results indicate that B.1.1.7 infection in African green monkeys is associated with increased respiratory replication and shedding but no disease enhancement similar to human B.1.1.7 cases. ONE-SENTENCE SUMMARY: UK B.1.1.7 infection of African green monkeys exhibits increased respiratory replication and shedding but no disease enhancement.

Animal models for Lassa virus infection.

In humans, Lassa virus infection can result in disease with hemorrhagic manifestations and high fatality rates. There are no approved treatments or vaccines available and the inherent danger of studying Lassa virus means it can only be studied in high containment labs (BSL4). Under these conditions, mouse models are becoming an important instrument in the study of Lassa virus infection, disease and host responses. While guinea pigs and non-human primates are the critical components in assessing treatments and vaccines and have recently been used with great affect in this capacity.

Virology. Mutation rate and genotype variation of Ebola virus from Mali case sequences.

The occurrence of Ebola virus (EBOV) in West Africa during 2013-2015 is unprecedented. Early reports suggested that in this outbreak EBOV is mutating twice as fast as previously observed, which indicates the potential for changes in transmissibility and virulence and could render current molecular diagnostics and countermeasures ineffective. We have determined additional full-length sequences from two clusters of imported EBOV infections into Mali, and we show that the nucleotide substitution rate (9.6 × 10(-4) substitutions per site per year) is consistent with rates observed in Central African outbreaks. In addition, overall variation among all genotypes observed remains low. Thus, our data indicate that EBOV is not undergoing rapid evolution in humans during the current outbreak. This finding has important implications for outbreak response and public health decisions and should alleviate several previously raised concerns.

Potential role for p53 in the permissive life cycle of human cytomegalovirus.

Infection of primary fibroblasts with human cytomegalovirus (HCMV) causes a rapid stabilization of the cellular protein p53. p53 is a major effector of the cellular damage response, and activation of this transcription factor can lead either to cell cycle arrest or to apoptosis. Viruses employ many tactics to avoid p53-mediated effects. One method HCMV uses to counteract p53 is sequestration into its viral replication centers. In order to determine whether or not HCMV benefits from this sequestration, we infected a p53(-/-) fibroblast line. We find that although these cells are permissive for viral infection, several parameters are substantially altered compared to wild-type (wt) fibroblasts. p53(-/-) cells show delayed and decreased accumulation of infectious viral particles compared to control fibroblasts, with the largest difference of 100-fold at 72 h post infection (p.i.) and peak titers decreased by approximately 10- to 20-fold at 144 h p.i. Viral DNA accumulation is also delayed and somewhat decreased in p53(-/-) cells; however, on average, levels of DNA are not more than fivefold lower than wt at any time p.i. and thus cannot account entirely for the observed differences in titers. In addition, there are delays in the expression of several key viral proteins, including the early replication protein UL44 and some of the late structural proteins, pp28 (UL99) and MCP (UL86). UL44 localization also indicates delayed formation and maturation of the replication centers throughout the course of infection. Localization of the major tegument protein pp65 (UL83) is also altered in these p53(-/-) cells. Partial reconstitution of the p53(-/-) cells with a wt copy of p53 returns all parameters toward wt, while reconstitution with mutant p53 does not. Taken together, our data suggest that wt p53 enhances the ability of HCMV to replicate and produce high concentrations of infectious virions in permissive cells.