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

Calanoid copepod zooplankton density is positively associated with water residence time across the continental United States

Inherent differences between naturally-formed lakes and human-made reservoirs may play an important role in shaping zooplankton community structure. For example, because many reservoirs are created by impounding and managing lotic systems for specific human purposes, zooplankton communities may be affected by factors that are unique to reservoirs, such as shorter water residence times and a reservoir's management regime, compared to natural lakes. However, the environmental factors that structure zooplankton communities in natural lakes vs. reservoirs may vary at the continental scale and remain largely unknown. We analyzed data from the 2007 U.S. Environmental Protection Agency's National Lakes Assessment and the U.S. Army Corps of Engineers' National Inventory of Dams to compare large-bodied crustacean zooplankton communities (defined here as individuals retained by 0.243 mm mesh size) in natural lakes and reservoirs across the continental U.S. using multiple linear regressions and regression tree analyses. We found that large-bodied crustacean zooplankton density was overall higher in natural lakes compared to reservoirs when the effect of latitude was controlled. The difference between waterbody types was driven by calanoid copepods, which were also more likely to be dominant in the >0.243 mm zooplankton community in natural lakes than in reservoirs. Regression tree analyses revealed that water residence time was not a major driver of calanoid copepod density in natural lakes but was one of the most important drivers of calanoid copepod density in reservoirs, which had on average 0.5-year shorter water residence times than natural lakes. Reservoirs managed for purposes that resulted in shorter residence times (e.g., hydroelectric power) had lower zooplankton densities than reservoirs managed for purposes that resulted in longer residence times (e.g., irrigation). Consequently, our results indicate that water residence time may be an important characteristic driving differing large-bodied zooplankton dynamics between reservoirs and natural lakes.publishe