Virion-associated US28 rapidly modulates Akt activity to suppress HCMV lytic replication in monocytes.

Establishing a non-productive quiescent/silent infection within monocytes is essential for spread of human cytomegalovirus (HCMV). Yet, how HCMV establishes a quiescent infection in monocytes remains unclear. US28 is a viral G protein-coupled receptor (GPCR) essential for silent infections within cells of the myeloid lineage. We found virion-associated US28 was rapidly delivered to monocytes, while de novo synthesized US28 was delayed for several days. A recombinant mutant virus lacking US28 (US28Δ) was unable to establish a quiescent infection, resulting in a fully productive lytic replication cycle. Mechanistically, viral entry of US28Δ phosphorylated Akt at both serine 473 (S473) and threonine 308 (T308), which contrasted with the site-specific phosphorylation of Akt at S473 following WT infection. Preventing Akt bi-phosphorylation prevented lytic replication of US28Δ, and ectopic expression of a constitutively phosphorylated Akt variant triggered lytic replication of WT infection. Our data demonstrate that virion-delivered US28 fine-tunes Akt activity to permit HCMV infection to enter a quiescent state following primary infection of monocytes.

Draft-genome analysis provides insights into the virulence properties and genome plasticity of Vibrio fluvialis organisms isolated from shrimp farms and Turag river in Bangladesh.

Vibrio fluvialis is an opportunistic waterborne and seafood-borne enteric pathogen capable of causing severe diarrhea leading to death. This pathogen is endemic to Bangladesh, a country which is a major producer of cultured shrimp and wild-caught prawns. In this study, we carried out whole-genome sequencing of three V. fluvialis organisms isolated from shrimp farm and river sediment showing strong pathogenic characteristics in vivo and in vitro and compared their genomes against other V. fluvialis and related pathogenic species to glean insights into their potential as pathogens. Numerous virulence-associated genes including hemolysins, cytolysins, three separate Type IV pili, Types II and VI secretion systems, biofilm, and the V. cholerae pathogenesis regulating gene, toxR, were identified. Moreover, we found strain S-10 to have the propensity to acquire antibiotic resistance genes through horizontal gene transfer. These findings indicate that shrimp farms and rivers could be potential sources of V. fluvialis organisms which are an infection threat of public health concern.