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An estimated 170 million people worldwide carry the hepatitis C virus (HCV), and in more developed countries the prevalence and incidence of HCV is particularly high among injecting drug users (IDUs). Spontaneous clearance of HCV infection and reinfection is well recognized but the level of protection against further infection conferred by HCV infection and clearance remains uncertain. We conducted a prospective study of HCV infection in IDUs recruited in Melbourne, Australia, using a much shorter median testing interval than in previous studies. Incidences of naive infection and reinfection were calculated by the person-year method and Cox proportional hazards regression used to adjust for covariates. A significantly higher HCV incidence rate was measured in previously infected IDUs (46.8% per year) compared with HCV-naive IDUs (15.5% per year). The hazard ratio for previously infected IDUs compared to HCV-naive IDUs, after adjustment for time-dependent covariates, was 2.54 (95% confidence interval, 1.11-5.78, P > ͦzͦ < 0.05). Viral persistence after reinfection appeared similar to that following naive infection. Conclusion: Our data suggest that HCV infection in IDUs is more likely following prior infection and clearance than in HCV-naive individuals, implying no increased immunity against further infection. This result has important implications for the future development of an HCV vaccine. T he hepatitis C virus (HCV) infects an estimated 170 million people worldwide, and is a significant cause of morbidity and mortality due to cirrhosis and hepatocellular carcinoma. 1 Injecting drug users (IDUs) are the population subgroup at greatest risk of HCV infection in more developed countries, with prevalence rates of 45% or greater per year 2,3 and incidence rates of 25% per year or higher being common. 4,5 HCV differs from the hepatitis B virus and many other infectious viral agents in that infection and the generation of an immune response does not necessarily protect an individual from HCV reinfection or superinfection. Whether infection with HCV and subsequent clearance is even partially protective against further infection is yet to be definitively resolved.In 2002, Mehta et al. 6 reported that previously infected IDUs were significantly less likely to be reinfected, even after accounting for risk behavior. Further reports supported this finding: Grebely et al. 7 reported a significantly lower incidence of HCV reinfection in IDUs than in naive individuals; and Dove et al. 8 detected no reinfections in a small group of ongoing IDUs with previous HCV clearance. A retrospective study by Micallef et al. 9 reported the incidence of HCV reinfection in IDUs was higher than naive infection-31 out of 100 person-years (PYs) (95% confidence interval [CI], 17-62) compared to 17 out of 100 PYs (95% CI, 14-2) although with adjustment for HCV risk behavior variables, the incidence ratio was only marginally greater and was not statistically significant (incidence rate ratio, 1.11; P ϭ 0.8).The importance of the reinfection is...

Replication complexes are membrane-bound cytoplasmic vacuoles involved in rubella virus (RV) replication. These structures can be identified by their characteristic morphology at the electron microscopy (EM) level and by their association with double-stranded (ds) RNA in immunogold labeling EM studies. Although these virus-induced structures bear some resemblance to lysosomes, their exact nature and origin are unknown. In this study, the localization of two lysosomal markers, lysosomal-associated membrane protein (Lamp-1) and acid phosphatase, relative to the replication complexes was examined by light and electron microscopy. Confocal microscopy using antibodies to dsRNA and Lamp-1 showed colocalization of these two markers in the cytoplasm of RV-infected cells. Immunogold labeling EM studies using antibodies to Lamp-1 confirmed that Lamp-1 was associated with RV replication complexes. EM histochemical studies demonstrated the presence of acid phosphatase in the vacuoles of RV replication complexes. Taken together, these studies show that RV replication complexes are virus-modified lysosomes.

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