Induction of CXCR3- and CCR5-associated chemokines during acute hepatitis C virus infection

Marija Zeremski, Giles Hooker, Marla A. Shu, Emily Winkelstein, Queenie Brown, Don Des Jarlais, Leslie H. Tobler, Barbara Rehermann, Michael P. Busch, Brian R. Edlin, Andrew H. Talal

Research output: Contribution to journalArticle

Abstract

Background & Aims: Characterization of inflammatory mediators, such as chemokines, during acute hepatitis C virus (HCV) infection might shed some light on viral clearance mechanisms. Methods: Plasma levels of CXCR3 (CXCL9-11)- and CCR5 (CCL3-4)-associated chemokines, ALT, and HCV RNA were measured in nine injection drug users (median 26 samples/patient) before and during 10 acute (eight primary and two secondary) HCV infections. Using functional data analysis, we estimated smooth long-term trends in chemokine expression levels to obtain the magnitude and timing of overall changes. Residuals were analyzed to characterize short-term fluctuations. Results: CXCL9-11 induction began 38-53 days and peaked 72-83 days after virus acquisition. Increases in ALT levels followed a similar pattern. Substantial negative auto-correlations of chemokine levels at 1 week lags suggested substantial week-to-week oscillations. Significant correlations were observed between CXCL10 and HCV RNA as well as ALT and CXCR3-associated chemokines measured in the preceding week, CCL3-4 expression levels did not change appreciably during acute HCV infection. Conclusions: Elevation of CXCR3-associated chemokines late during acute HCV infection suggests a role for cellular immune responses in chemokine induction. Week-to-week oscillations of HCV RNA, chemokines, and ALT suggest frequent, repeated cycles of gain and loss of immune control during acute hepatitis C.

Original languageEnglish (US)
Pages (from-to)545-553
Number of pages9
JournalJournal of Hepatology
Volume55
Issue number3
DOIs
StatePublished - Sep 1 2011

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Virus Diseases
Chemokines
Hepacivirus
RNA
Hepatitis C
Drug Users
Cellular Immunity
Viruses
Injections

Keywords

  • CCL3
  • CCL4
  • CXCL10
  • CXCL11
  • CXCL9
  • Inflammation

ASJC Scopus subject areas

  • Hepatology

Cite this

Induction of CXCR3- and CCR5-associated chemokines during acute hepatitis C virus infection. / Zeremski, Marija; Hooker, Giles; Shu, Marla A.; Winkelstein, Emily; Brown, Queenie; Des Jarlais, Don; Tobler, Leslie H.; Rehermann, Barbara; Busch, Michael P.; Edlin, Brian R.; Talal, Andrew H.

In: Journal of Hepatology, Vol. 55, No. 3, 01.09.2011, p. 545-553.

Research output: Contribution to journalArticle

Zeremski, M, Hooker, G, Shu, MA, Winkelstein, E, Brown, Q, Des Jarlais, D, Tobler, LH, Rehermann, B, Busch, MP, Edlin, BR & Talal, AH 2011, 'Induction of CXCR3- and CCR5-associated chemokines during acute hepatitis C virus infection', Journal of Hepatology, vol. 55, no. 3, pp. 545-553. https://doi.org/10.1016/j.jhep.2010.12.033
Zeremski, Marija ; Hooker, Giles ; Shu, Marla A. ; Winkelstein, Emily ; Brown, Queenie ; Des Jarlais, Don ; Tobler, Leslie H. ; Rehermann, Barbara ; Busch, Michael P. ; Edlin, Brian R. ; Talal, Andrew H. / Induction of CXCR3- and CCR5-associated chemokines during acute hepatitis C virus infection. In: Journal of Hepatology. 2011 ; Vol. 55, No. 3. pp. 545-553.
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AU - Des Jarlais, Don

AU - Tobler, Leslie H.

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AB - Background & Aims: Characterization of inflammatory mediators, such as chemokines, during acute hepatitis C virus (HCV) infection might shed some light on viral clearance mechanisms. Methods: Plasma levels of CXCR3 (CXCL9-11)- and CCR5 (CCL3-4)-associated chemokines, ALT, and HCV RNA were measured in nine injection drug users (median 26 samples/patient) before and during 10 acute (eight primary and two secondary) HCV infections. Using functional data analysis, we estimated smooth long-term trends in chemokine expression levels to obtain the magnitude and timing of overall changes. Residuals were analyzed to characterize short-term fluctuations. Results: CXCL9-11 induction began 38-53 days and peaked 72-83 days after virus acquisition. Increases in ALT levels followed a similar pattern. Substantial negative auto-correlations of chemokine levels at 1 week lags suggested substantial week-to-week oscillations. Significant correlations were observed between CXCL10 and HCV RNA as well as ALT and CXCR3-associated chemokines measured in the preceding week, CCL3-4 expression levels did not change appreciably during acute HCV infection. Conclusions: Elevation of CXCR3-associated chemokines late during acute HCV infection suggests a role for cellular immune responses in chemokine induction. Week-to-week oscillations of HCV RNA, chemokines, and ALT suggest frequent, repeated cycles of gain and loss of immune control during acute hepatitis C.

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