Long-term evolution of the hypervariable region of hepatitis C virus in a common-source-infected cohort

The long-term evolution of the hepatitis C virus hypervariable region (HVR) and flanking regions of the E1 and E2 envelope proteins have been studied in a cohort of women infected from a common source of anti-D immunoglobulin. Whereas virus sequences in the infectious source were relatively homogeneous, distinct HVR variants were observed in each anti-D recipient, indicating that this region can evolve in multiple directions from the same point. Where HVR variants with dissimilar sequences were present in a single individual, the frequency of synonymous substitution in the flanking regions suggested that the lineages diverged more than a decade previously. Even where a single major HVR variant was present in an infected individual, this lineage was usually several years old. Multiple lineages can therefore coexist during long periods of chronic infection without replacement. The characteristics of amino acid substitution in the HVR were not consistent with the random accumulation of mutations and imply that amino acid replacement in the HVR was strongly constrained. Another variable region of E2 centered on codon 60 shows similar constraints, while HVR2 was relatively unconstrained. Several of these features are difficult to explain if a neutralizing immune response against the HVR is the only selective force operating on E2. The impact of PCR artifacts such as nucleotide misincorporation and the shuffling of dissimilar templates is discussed

Continuous arterial spin labeling at the human common carotid artery: the influence of transit times.

In evaluating the sensitivity of arterial spin labeling (CASL) and for quantification of perfusion, knowledge of the transit time from the labeling plane to the imaging slice is crucial. The purpose of the current study was to obtain estimates of transit times relevant under the specific experimental conditions of CASL in human subjects using a separate local labeling coil at the neck. Specifically, the post-label delay (PLD), i.e. the time between the end of the labeling period and the image acquisition, was varied either with or without additional application of crusher gradients to suppress intravascular signal contributions. The overall sensitivity change for varying the PLD between 1000 and 1700 ms was low. A tissue transit time from the neck to an axial supraventricular section through Broca's knee was obtained by fitting the PLD dependence to a two-compartment model. Averaging over subjects yielded 1930 +/- 110 ms for the tissue transit time, and 73 +/- 5 ml min(-1) 100 g(-1) for the cerebral blood flow. Small areas that exhibited a very high signal change upon labeling were indicative of regional variation in cerebral blood flow related to vascular anatomy