Protein Kinase PKR Mediates the Apoptosis Induction and Growth Restriction Phenotypes of C Protein-Deficient Measles Virus

The measles virus (MV) accessory proteins V and C play important roles in MV replication and pathogenesis. Infection with recombinant MV lacking either V or C causes more cell death than infection with the parental vaccine-equivalent virus (MVvac), and C-deficient virus grows poorly relative to the parental virus. Here, we show that a major effector of the C phenotype is the RNA-dependent protein kinase PKR. Using human HeLa cells stably deficient in PKR as a result of RNA interference-mediated knockdown (PKR^kd cells), we demonstrated that a reduction in PKR partially rescued the growth defect of C knockout (C^ko) virus but had no effect on the growth of either wild-type (WT) or V knockout (V^ko) virus. Increased growth of the C^ko virus in PKR^kd cells correlated with increased viral protein expression, while defective growth and decreased protein expression in PKR-sufficient cells correlated with increased phosphorylation of PKR and the α subunit of eukaryotic initiation factor 2. Furthermore, infection with WT, V^ko, or especially C^ko virus caused significantly less apoptosis in PKR^kd cells than in PKR-sufficient cells. Although apoptosis induced by C^ko virus infection in PKR-sufficient cells was blocked by a caspase antagonist, the growth of C^ko virus was not restored to the WT level by treatment with this pharmacologic inhibitor. Taken together, these results indicate that PKR plays an important antiviral role during MV infection but that the virus growth restriction by PKR is not dependent upon the induction of apoptosis. Furthermore, the results establish that a principal function of the MV C protein is to antagonize the proapoptotic and antiviral activities of PKR.     

Epsilonematidae (Nematoda) from a cold-water coral environment in the Porcupine Seabight, with a discussion on the status of the genus Metaglochinema Gourbault & Decraemer, 1986

Thirteen species of nematodes from the family Epsilonematidae Steiner, 1927 were found to be associated with a cold-water coral reef in the Porcupine Seabight. Among them, four species were already known from various locations such as Chile and Papua New Guinea. Three new species are described here: Glochinema trispinatumsp. n. is recognized by three dorsal thorns in the pharyngeal region. This species was also recovered from the Antarctic shelf. Epsilonema multispiralumsp. n. is characterised by a multispiral amphid consisting of 3.25 coils. Bathyepsilonema lopheliaesp. n. is characterised by its body length, the position and relative width of the amphids and the nature of the cuticular ornamentation. Within the subfamily Glochinematinae Lorenzen, 1974, the number and arrangement of ambulatory setae is considered not to be of diagnostic importance. The former species Metaglochinema strigosumGourbault & Decraemer, 1993 is therefore classified under the genus GlochinemaLorenzen, 1974. The original genus diagnosis of Metaglochinema, now a monotypic genus, is adjusted. The geographic distribution of epsilonematid nematodes is briefly discussed.     

Evolution of Sickness and Healing

Evolution of Sickness and Healing. Horacio Fábrega Jr. Berkeley: University of California Press, 1997 (cloth), xv. 364pp.     

Genome-wide CRISPR Screens Reveal Host Factors Critical for SARS-CoV-2 Infection

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Environmentally constrained mutation and adaptive evolution in Salmonella

The relationship between environment and mutation is complex [1]. Claims of Lamarkian mutation [2] have proved unfounded [3], [4] and [5]; it is apparent, however, that the external environment can influence the generation of heritable variation, through either direct effects on DNA sequence [6] or DNA maintenance and copying mechanisms [7], [8], [9] and [10], or as a consequence of evolutionary processes [11], [12], [13], [14], [15] and [16]. The spectrum of mutational events subject to environmental influence is unknown [6] and precisely how environmental signals modulate mutation is unclear. Evidence from bacteria suggests that a transient recombination-dependent hypermutational state can be induced by starvation [5]. It is also apparent that chnages in the mutability of specific loci can be influenced by alterations in DNA topology [10] and [17]. Here we describe a remarkable instance of adaptive evolution in Salmonella which is caused by a mutation that occurs in intermediate-strength osmotic environments. We show that the mutation is not ‘directed’ and describe its genetic basis. We also present compelling evidence in support of the hypothesis that the mutational event is constrained by signals transmitted from the external environment via changes in the activity of DNA gyrase.