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Advanced molecular surveillance of hepatitis C virus.

ABSTRACT: Hepatitis C virus (HCV) infection is an important public health problem worldwide. HCV exploits complex molecular mechanisms, which result in a high degree of intrahost genetic heterogeneity. This high degree of variability represents a challenge for the accurate establishment of genetic relatedness between cases and complicates the identification of sources of infection. Tracking HCV infections is crucial for the elucidation of routes of transmission in a variety of settings. Therefore, implementation of HCV advanced molecular surveillance (AMS) is essential for disease control. Accounting for virulence is also important for HCV AMS and both viral and host factors contribute to the disease outcome. Therefore, HCV AMS requires the incorporation of host factors as an integral component of the algorithms used to monitor disease occurrence. Importantly, implementation of comprehensive global databases and data mining are also needed for the proper study of the mechanisms responsible for HCV transmission. Here, we review molecular aspects associated with HCV transmission, as well as the most recent technological advances used for virus and host characterization. Additionally, the cornerstone discoveries that have defined the pathway for viral characterization are presented and the importance of implementing advanced HCV molecular surveillance is highlighted.

SUBMITTER: Rossi LM

PROVIDER: S-EPMC4379565 | biostudies-literature | 2015 Mar

REPOSITORIES: biostudies-literature

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Advanced molecular surveillance of hepatitis C virus.

Rossi Livia Maria Gonçalves LM Escobar-Gutierrez Alejandro A Rahal Paula P

Viruses 20150313 3

Hepatitis C virus (HCV) infection is an important public health problem worldwide. HCV exploits complex molecular mechanisms, which result in a high degree of intrahost genetic heterogeneity. This high degree of variability represents a challenge for the accurate establishment of genetic relatedness between cases and complicates the identification of sources of infection. Tracking HCV infections is crucial for the elucidation of routes of transmission in a variety of settings. Therefore, impleme ...[more]

PMID: 25781918

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Project description:Outbreaks of the emerging arbovirus chikungunya virus (CHIKV) affect millions of individuals in Asia, Africa, and Latin America. Vector competence can be changed dramatically by single amino acid exchanges located predominantly within the CHIKV E1 and E2 envelope proteins, which are associated with enhanced transmissibility by anthropophilic Aedes mosquitoes. Commonly used reference assays for molecular surveillance cover only a few adaptive mutations within the envelope domains and have not been validated for all CHIKV genotypes. The recognized landscape of CHIKV adaptive mutations is thus likely incomplete. We designed two nested reverse transcription-PCR (RT-PCR) assays that cover hot spots of viral adaptation to vectors within the E1 and E2 genomic domains. Primers were designed in conserved genomic regions to allow broad usability across CHIKV genotypes. The sensitivity of both assays was at least equivalent to E1- and E2-based reference assays and robust among CHIKV genotypes at 51.4 IU/reaction (E1, 95% confidence interval [CI], 39.8 to 78.9) and 4.0 IU/reaction (E2, 95% CI, 2.0 to 7.4). Upon analysis of the complete known CHIKV genomic diversity, up to 11 nucleotide mismatches with CHIKV variants occurred under oligonucleotide binding sites of reference assays, potentially limiting assay sensitivity, whereas no critical mismatches occurred in the new assays. Specificity testing with nine alphaviruses representing all serocomplexes showed amplification of Mayaro virus and O'nyong-nyong virus by the E1-based assay, but not by the E2-based assay. The high sensitivity and specificity of the new E2-based assay may allow its diagnostic usage in resource-limited settings. The combined new assays allow improved molecular epidemiological surveillance of CHIKV globally.IMPORTANCE The life cycle of arboviruses relies on efficient infection of and transmission by arthropod vectors. Adaptation to new vectors can thus dramatically increase the geographic range of an arbovirus. Several adaptive mutations enhance chikungunya virus (CHIKV) transmissibility by different mosquito species. The appearance of those adaptive mutations has led to large-scale CHIKV outbreaks in Asia, Africa, and Europe. Molecular surveillance of circulating CHIKV strains for adaptive mutations contributes to precise risk assessments and efficient vector control and provides new insight into the evolution of vector adaptation. Existing assays for molecular CHIKV surveillance are limited by poor coverage of known adaptive mutations, low sensitivity, and cost-intensive deep sequencing approaches, preventing universal application. We developed two highly sensitive nested RT-PCR assays that cover hot spots of vector adaptation in CHIKV envelope domains. The new assays allow unprecedented molecular surveillance across all CHIKV genotypes and diagnostic use in resource-limited settings globally.

Project description:BackgroundIn Uzbekistan, routine serologic testing has not been available to differentiate etiologies of acute viral hepatitis (AVH). To determine the age groups most affected by hepatitis E virus (HEV) during documented AVH epidemics, trends in AVH-associated mortality rate (MR) per 100,000 over a 15-year period and reported incidence of AVH over a 35-year period were examined.MethodsReported AVH incidence data from 1971 to 2005 and AVH-associated mortality data from 1981 to 1995 were examined. Serologic markers for infection with hepatitis viruses A, B, D, and E were determined from a sample of hospitalized patients with AVH from an epidemic period (1987) and from a sample of pregnant women with AVH from a non-epidemic period (1992).ResultsTwo multi-year AVH outbreaks were identified: one during 1975-1976, and one during 1985-1987. During 1985-1987, AVH-associated MRs were 12.3-17.8 per 100,000 for the general population. Highest AVH-associated MRs occurred among children in the first 3 years of life (40-190 per 100,000) and among women aged 20-29 (15-21 per 100,000). During 1988-1995 when reported AVH morbidity was much lower in the general population, AVH-associated MRs were markedly lower among these same age groups. In 1988, AVH-associated MRs were higher in rural (21 per 100,000) than in urban (8 per 100,000) populations (RR 2.6; 95% CI 1.16-5.93; p < 0.05). Serologic evidence of acute HEV infection was found in 280 of 396 (71%) patients with AVH in 1987 and 12 of 99 (12%) pregnant patients with AVH in 1992.ConclusionIn the absence of the availability of confirmatory testing, inferences regarding probable hepatitis epidemic etiologies can sometimes be made using surveillance data, comparing AVH incidence with AVH-associated mortality with an eye to population-based viral hepatitis control measures. Data presented here implicate HEV as the probable etiology of high mortality observed in pregnant women and in children less than 3 years of age in Uzbekistan during 1985-1987. High mortality among pregnant women but not among children less than 3 years has been observed in previous descriptions of epidemic hepatitis E. The high mortality among younger children observed in an AVH outbreak associated with hepatitis E merits corroboration in future outbreaks.

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Advanced molecular surveillance of hepatitis C virus.

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Advanced molecular surveillance of hepatitis C virus.

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