T cell responses and viral variability in blood donation candidates with occult hepatitis B infection

Bes, Marta; Vargas, Vı́ctor; Pirón, María; Casamitjana, Natàlia; Esteban, Juan Ignacio; Vilanova, Núria; Pinacho, A.; Quer, Josep; Puig, Lluís; Guàrdia, J; Sauleda, Sílvia

doi:10.1016/j.jhep.2011.11.011

Cited by 63 publications

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References 44 publications

(79 reference statements)

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“…4 Within this context, we observed that SHRs presented a higher magnitude of HBcAg-specific T-cell responses (Stimulation Index (SI)5SI562.3, P,0.0001) in comparison to HBV carriers (SI525.4) and OBI cases (SI526.2).…”

mentioning

confidence: 89%

KIR and a specific HLA-C gene are associated with susceptibility and resistance to hepatitis B virus infection in a Brazilian population

et al. 2014

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mentioning

confidence: 89%

KIR and a specific HLA-C gene are associated with susceptibility and resistance to hepatitis B virus infection in a Brazilian population

et al. 2014

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“…ultiple exposures to small amounts of hepatitis B virus (HBV) are of frequent occurrence in both occupational and nonoccupational settings (1)(2)(3)(4)(5)(6). Routine vaccination against HBV prevents infection potentially caused by such exposure.…”

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confidence: 99%

Repeated Exposure to Trace Amounts of Woodchuck Hepadnavirus Induces Molecularly Evident Infection and Virus-Specific T Cell Response in the Absence of Serological Infection Markers and Hepatitis

Gujar

Mulrooney‐Cousins

Michalak

2013

J Virol

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Exposure to multiple small doses of hepatitis B virus (HBV) is a frequent occurrence in high-risk groups, including close relatives of infected individuals, primary care givers, and intravenous drug users. It remains uncertain whether such repeated contact may culminate in a symptomatic infection coinciding with hepatitis in individuals not immunoprotected. In this study, we evaluated consequences of multiple exposures to small, liver-nonpathogenic amounts of infectious hepadnavirus in the woodchuck model of hepatitis B. Virus-naïve animals were intravenously injected with 6 weekly doses of 110 DNase digestion-protected virions of woodchuck hepatitis virus (WHV), injected again with 6 weekly 110-virion doses after 7.5 months, and then challenged or not with a liver-pathogenic dose of 1.1 ؋ 10 6 virions of the same inoculum. The data revealed that two rounds of such repeated exposure did not result in serologically evident infection or hepatitis. However, a low-level WHV DNA-positive infection accompanied by a WHV-specific T cell response in the absence of antiviral antibody reactivity was established. The kinetics of the virus-specific and mitogen-induced (generalized) T cell responses and the inability to induce immunoprotection against challenge with a large, liver-pathogenic virus dose were closely comparable to those previously reported for occult infection initiated by a single liver-nonpathogenic dose of WHV. Thus, repeated exposures to small quantities of hepadnavirus induce molecularly evident but serologically silent infection that does not culminate in hepatitis or generate immune protection. The findings imply that the HBV-specific T cell response encountered in the absence of serological markers of infection likely reflects ongoing occult infection. Multiple exposures to small amounts of hepatitis B virus (HBV) are of frequent occurrence in both occupational and nonoccupational settings (1-6). Routine vaccination against HBV prevents infection potentially caused by such exposure. However, consequences of repeated contacts with small quantities of HBV of individuals not immunoprotected against the virus are not recognized and it is unknown whether such exposure can culminate in a serologically detectable infection and hepatitis.The data acquired from the woodchuck model of hepatitis B showed that exposure to a singular low dose (i.e., Ͻ1,000 virions) of woodchuck hepatitis virus (WHV), which is a close relative of HBV (7-9), establishes serologically undetectable infection in which the virus genome and its replication are detectable when nucleic acid amplification assays of enhanced sensitivity are applied (10-13). This molecularly evident but immunovirologically silent infection was designated primary occult infection (POI) (12,14). POI was originally uncovered in offspring born to woodchuck dams convalescent from experimental acute hepatitis (AH) (15). In these animals, WHV DNA was identified in serum and in the immune system but not in the liver and virus replication progressed at a very low level ...

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“…When screening donors blood, this is especially important, since donor blood is used mainly in patients with severe course of various diseases characterized by increased susceptibility to HBV against immunosuppression. The importance of detecting OHB in the population and in blood donors was also shown in the study of a specific immune response, where the severity of the Th1 response in patients with OHB was significantly higher than in patients with symptomatic CHBV in the phase of inactive HBV carrier [14,50].…”

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confidence: 95%

RESULTS OF GENOTYPING HEPATITIS VIRUS B IN HBsAg-NEGATIVE BLOOD DONORS IN ASTANA, KAZAKHSTAN

Ostankova

Семенов

Буркитбаев

et al. 2018

Russian Journal of Infection and Immunity

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Abstract. The prevalence of HBV infection is estimated by the frequency of occurrence of HBsAg and varies depending on the geographic region. Chronic infection is characterized by a stable presence of HBsAg for 6 months, with the exception of the occult form of the disease, characterized by the absence of HBsAg, an extremely low level of HBV DNA in the blood serum. The problem of identifying occult HBV (ocHBV) is especially relevant because of the development of transplantology and transfusiology. However, serological screening of donor blood used in the Russian Federation and Central Asian countries does not reveal HBV seronegative donors. Since HBV infection is possible with the introduction of small doses of the virus, the importance of using complex molecular methods for detecting donor ocHBV is obvious, despite the low viral load, since donor blood is used predominantly in patients with severe course of various diseases characterized by increased susceptibility to HBV because of immunosuppression. The aim of our work was to study the characteristics of the genetic structure of the ocHBV in donors in Astana, Kazakhstan. A total of 500 blood plasma samples from HBsAg-negative donors were obtained in 2012 from residents of Kazakhstan, Astana. Using the method, we proposed to detect HBV DNA with a low viral load, HBV was detected in 9.4% of donors. Serological markers were found in 12.7% of patients with HBV DNA, 8.5% had HBcor IgG antibodies, 4.2% had HBcor IgG and HBe IgG antibodies at the same time. Thus, in 41 (87.3%) of the blood donor, ocHBV was seronegative. Based on the phylogenetic analysis of the 47 isolates showed that the HBV of genotype D (95.75%) prevails in the examined group in comparison with HBV of genotype A (4.25%). HBV subgenotypes are represented in the following ratios: D1 -46.8%, D2 -17.05%, D3 -31.9%, A2 -4.25%. In a comparative analysis, the distribution of HBV subgenotypes in the group with ocHBV and in the case of the manifest form in donors in the Republic of Kazakhstan significantly differed -χ 2 = 14.027 at p = 0.0072, d f = 4. The incidence of HBV D3 with ocHBV (31.9%) exceeded that of patients with a manifest form (7.4%). The relative risk of occult form of disease in patients with the subgenotype D3 is significantly higher (RR = 1.572, CI: 1.179-2.096, p = 0.0208). When assessing the picture of HBV diversity on the material of the group including HBsAg-negative and HBsAg-positive blood donors, it is evident that the genetic relationship of the manifestations of the manifest HBV and the ocHBV of genotype D is obvious. Among the isolates are both similar in nucleotide sequences with those previously described in various regions of Europe and Central Asia, and circulating in the territory of the Republic of Kazakhstan, which indicates an independent homologous evolution of HBV in the region. The high incidence of ocHBV among HBsAg-negative blood donors is indicative not only of the widespread prevalence of the occult form of the disease course in the population and the inadequacy ...

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T cell responses and viral variability in blood donation candidates with occult hepatitis B infection

Cited by 63 publications

References 44 publications

KIR and a specific HLA-C gene are associated with susceptibility and resistance to hepatitis B virus infection in a Brazilian population

KIR and a specific HLA-C gene are associated with susceptibility and resistance to hepatitis B virus infection in a Brazilian population

Repeated Exposure to Trace Amounts of Woodchuck Hepadnavirus Induces Molecularly Evident Infection and Virus-Specific T Cell Response in the Absence of Serological Infection Markers and Hepatitis

RESULTS OF GENOTYPING HEPATITIS VIRUS B IN HBsAg-NEGATIVE BLOOD DONORS IN ASTANA, KAZAKHSTAN

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