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Pakistan-US Science and Technology Cooperation Program                                                            
Phase 3 (2007 Deadline)

Hepatitis C Virus Management in Pakistan   

Charles M. Rice, The Rockefeller University, New York
Ishtiaq Qadri, (formerly) National University of Sciences and Technology, Islamabad
Pakistani Funding (HEC):  $ 300,000
US Funding (State):   $ 250,000
Project Dates on US Side: July 1, 2008 - June 30, 2012

Project Overview

The overall objective of this grant is to broaden the understanding and management of the Hepatitis C virus (HCV) pandemic in Pakistan. One of the initial goals is to develop HCV models that better represent the genotype 3 virus that predominates in Pakistan. The majority of tools used to study HCV biology represent viruses from either genotype 1 or 2. It is clear from these studies that there will be genotype-specific treatment effects; however, it remains to be delineated what these effects will be for genotype 3. This research team has been working towards better describing the HCV variants circulating in Pakistan and developing tools to specifically characterize genotype 3 virus.

Major Results

  • Provided training to 18 students and researchers, including facilitating the visit and training of a female Pakistani scientist in the US partner’s lab
  • Organized the 1st International HCV Management Symposium, held at NUST February 10-11, 2011 
  • Established the Diagnostic Lab at the NUST Center of Virology and Immunology
  • Developed HCV intergenotypic chimeras, robust in vitro serine protease FRET-based assay, HCV NS3 helicase Assay, and an ELISA-based in vitro infectivity assay for HCV, with a patent application submitted to the Intellectual Property office at NUST
  • Developed and tested HCV pseudotype particles (HCVpp) for HCVpp production and infectivity
  • Published seven papers resulting from the project
  • Obtained additional funding from the Pakistani Higher Education Commission and the Centre National de la Recherche Scientifique

Quarterly Update

In the second quarter of 2011, Dr. Mohsan Saeed, a Pakistani postdoctoral fellow who recently completed his PhD in Japan, began his visit to Dr. Rice’s lab. He cataloged the clinical samples Dr. Rice had received from Dr. Qadri and did RNA load measurements on those reported by the Pakistani researchers to have the highest titers. Selected samples were subjected to further analyses, including (1) troubleshooting plasma samples with various anticoagulants to optimize conditions for infection of primary liver cells and (2) testing of Pakistani isolates for cell culture infectivity. The research team expects to create a battery of functional systems for Pakistani genotype 3a isolates that can be used to evaluate new antiviral therapies for this prevalent genotype in the next few months. High on the list of priorities will be to create a genotype 3a replicon, which would be the workhorse for compound screening and evaluation. Dr. Saeed’s experience in accomplishing this for a non-Pakistani genotype 3a isolate in the latter part of his PhD thesis work should be a great asset as he works with Dr. Rice and his colleagues on this new research effort. To accomplish the remaining project objectives, Dr. Rice has received a one year no-cost extension on his grant through June 30, 2012.

Progress Report Summaries

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