Inferring Viral Dynamics in Chronically HCV Infected Patients from the Spatial Distribution of Infected Hepatocytes

• DOI: 10.1371/journal.pcbi.1003934
• Publication Date: 2014-11-13T14:11:48Z
• Authors: Frederik Graw; Ashwin Balagopal; Abraham J. Kandathil; Stuart C. Ray; David L. Thomas; Ruy M. Ribeiro; Alan S. Perelson
• Keywords: Adult; Male; 0301 basic medicine; QH301-705.5; Computational Biology; Hepacivirus; Laser Capture Microdissection; Middle Aged; Hepatitis C; Models, Biological; 3. Good health; 03 medical and health sciences; Liver; Host-Pathogen Interactions; Hepatocytes; Humans; Female; Biology (General); Single-Cell Analysis; Algorithms; Research Article

Chronic liver infection by hepatitis C virus (HCV) is a major public health concern. Despite partly successful treatment options, several aspects of intrahepatic HCV dynamics are still poorly understood, including the preferred mode viral propagation, as well proportion infected hepatocytes. Answers to these questions have important implications for development therapeutic interventions. In this study, we present methods analyze spatial distribution hepatocytes obtained single cell laser capture microdissection from biopsy samples patients chronically with HCV. By characterizing internal structure clusters cells, able evaluate hypotheses about dynamics. We found that individual on range in size cells. addition, RNA content cluster declines presumably founded cells at maximal extension. These observations support idea seeded randomly (e.g. blood) and then spreads locally. Assuming amount intracellular proxy how long has been infected, estimate based models replication accumulation average less than week. Further, do not find relationship between estimated expansion time. Our method represents novel approach make inferences solid tissues static data.