Human cytomegalovirus infection in humanized liver chimeric mice. Issue 6 (26th February 2013)

• Record Type: Journal Article
• Authors: Kawahara, Toshiyasu; Lisboa, Luiz Filipe; Cader, Sonia; Douglas, Donna N.; Nourbakhsh, Mahra; Pu, Christopher H.; Lewis, Jamie T.; Churchill, Thomas A.; Humar, Atul; Kneteman, Norman M.
• Is Part Of: Hepatology research. Volume 43:Issue 6(2013:Jun.)
• Page Start: 679
• Page End: 684
• Publication Date: 2013-02-26
• Subjects: Liver -- Diseases -- Periodicals; Liver Diseases -- Periodicals; Foie -- Maladies -- Périodiques; 616.362
• DOI: 10.1111/j.1872-034X.2012.01116.x
• Languages: English
• ISSNs: 1386-6346

Abstract

<abstract abstract-type="main"> <title> <x xml:space="preserve">Abstract</x> </title> <sec id="hepr1116-sec-0001" sec-type="section"> <title>Aim</title> <p>Cytomegalovirus is a common viral pathogen that influences the outcome of organ transplantation. To date, there is no established method to evaluate the effects of human CMV (HCMV) treatments <italic>in vivo</italic> except for human clinical trials. In the current study, we describe the development of a mouse model that supports the <italic>in vivo</italic> propagation of HCMV.</p> </sec> <sec id="hepr1116-sec-0002" sec-type="section"> <title>Methods</title> <p>One million viable human hepatocytes, purified from human livers, were injected into the spleens of severe combined immunodeficient/albumin linked‐urokinase type plasminogen activator transgenic mice. A clinical strain of HCMV was inoculated in mice with confirmed human hepatocyte engraftment or in non‐chimeric controls. Infection was monitored through HCMV titers in the plasma. Mice were administrated ganciclovir (50 mg/kg per day, i.p.) beginning at 2 days post‐HCMV inoculation, or human liver natural killer (NK) cells (20 × 10<sup>6</sup> cells/mouse, i.v.) 1 day prior to HCMV inoculation.</p> </sec> <sec id="hepr1116-sec-0003" sec-type="section"> <title>Results</title> <p>Chimeric mice that received HCMV showed high plasma titers of HCMV DNA on days 1 and 6 that became undetectable by day 11 post‐inoculation. In contrast, non‐transplanted mice had only residual plasma inoculum detection at day 1 and no detectable viremia thereafter. The levels of HCMV DNA were reduced by ganciclovir treatment or by human liver NK cell adoptive transfer, while HCMV‐infected chimeric mice that were not treated sustained viremia during the follow up.</p> </sec> <sec id="hepr1116-sec-0004" sec-type="section"> <title>Conclusion</title> <p>Human liver chimeric mice provide an <italic>in vivo</italic> model for the study of acute HCMV infection of hepatocytes.</p> </sec> </abstract>