Neutralization of Pseudotyped Vesicular Stomatitis Virus Expressing Hepatitis C Virus Envelope Glycoprotein 1 or 2 by Serum from Patients

L. Martin Lagging .) 1 2 Keith Meyer 0 1 Johan Westin 1 Rune Wejst al 1 Gunnar Norkrans 1 Magnus Lindh 1 2 Ranjit Ray 0 1 0 Infectious Diseases and Immunology, Saint Louis University , St. Louis, Missouri 1 Received 29 August 2001; revised 3 December 2001; electronically pub- lished 1 April 2002. Presented in part: 8th International Symposium on Hepatitis C and Related Viruses , 2-5 September 2001, Paris , France ( abstract P-204). This study has been reviewed and approved by the Medical Faculty Ethical Research Committee of Go teborg University , Go teborg , Sweden. The human experimentation guidelines of the US Department of Health and Human Ser- vices were followed throughout the study. Financial support: Go teborg Medical Society; Swedish National Board of Health and Welfare Travel Funds; Sahlgrenska University Hospital Research Fund; Go teborg University Travel Fund; Folke Nordbring Foundation; Na- tional Institutes of Health (DK58023 and AI45250). Go teborg University , Guldhedsgatan 10B, S-413 46 Go teborg, Sweden (martin 2 Clinical Virology, Go teborg University , Go teborg , Sweden Infection with hepatitis C virus (HCV) generally progresses to chronic disease, although a minority of patients appear to clear viremia spontaneously. In this investigation, serum samples were analyzed for virological parameters, serum alanine aminotransferase (ALT) levels, and neutralizing antibody response against pseudotyped vesicular stomatitis virus (VSV) generated using chimeric envelope glycoprotein 1 (E1) or 2 (E2) of HCV. Testing of sequential serum samples that were collected beginning at the onset of acute-phase disease demonstrated intermittent viremia, elevated ALT levels, and detectable neutralization activity against VSV in 9 of 10 patients. Serum neutralization activity did not exhibit a correlation with the genotype of the infecting HCV or with virus load. On the other hand, patients with chronic HCV infection consistently had detectable amounts of virus present but no significant variation in ALT levels, and serum samples from a majority (. 90%) of patients failed to show detectable neutralization activity. - Materials and Methods Results Discussion Patient no., serum sample no. Nosocomial IVDU 3 3 Age at onset of infection, years Route of infection Normalized ALT levela Neutralization activity titer Virus load, IU/mL 78,000 3,000,000 4,700,000 Undetectable Undetectable 700,000 700,000 Undetectable 30,000 Undetectable 2500 230,000 21,000 Undetectable 3,300,000 440,000 Undetectable Undetectable 110,000 1,200,000 Undetectable 63,000 140,000 Undetectable 23,000 1,600,000 270,000 Undetectable 150,000 Undetectable 13,000 Undetectable 17,000 27,000 1700 , 1:10 , 1:10 , 1:10 , 1:10 , 1:10 , 1:10 , 1:10 , 1:10 , 1:10 , 1:10 , 1:10 , 1:10 , 1:10 , 1:10 , 1:10 Route of infection 1b 3b 1 1 1 NC 3 2 3b 1 1 3 1 1 NC 3 1 2 1 1 2b 1 1 3 2 NC 1 3 3 1 1 1 Patient no. Polymerase chain reaction result Duration of infection, years Normalized ALT levela Acknowledgments (...truncated)