While most adults are able to clear acute hepatitis B virus (HBV) infection, chronic HBV infection is recalcitrant to current therapy because of the persistence of covalently closed circular DNA in the nucleus. Complete clearance of the virus in these patients is rare, and long-term therapy with interferon and/or nucleoside analogues may be required in an attempt to suppress viral replication and prevent progressive liver damage. The difficulty of establishing HBV infection in cell culture and experimental organisms has hindered efforts to elucidate details of the HBV life cycle, but it has also revealed the importance of the cellular microenvironment required for HBV binding and entry. Recent studies have demonstrated an essential role of sodium-taurocholate cotransporting polypeptide as a functional receptor in HBV infection, which has facilitated the development of novel infection systems and opened the way for more detailed understanding of the early steps of HBV infection as well as a potential new therapeutic target. However, many gaps remain in understanding of how HBV recognizes and attaches to hepatocytes prior to binding to sodium-taurocholate cotransporting polypeptide, as well as events that are triggered after binding, including entry into the cell, intracellular transport, and passage through the nuclear pore complex. This review summarizes current knowledge of the initial stages of HBV infection leading to the establishment of covalently closed circular DNA in the nucleus.
Abstract. The immune response to dengue virus (DENV) infection generates high levels of antibodies (Abs) against the DENV non-structural protein 1 (NS1), particularly in cases of secondary infection. Therefore, anti-NS1 Abs may play a role in severe dengue infections, possibly by interacting (directly or indirectly) with host factors or regulating virus production. If it does play a role, NS1 may contain epitopes that mimic those epitopes of host molecules. Previous attempts to map immunogenic regions within DENV-NS1 were undertaken using mouse monoclonal Abs (MAbs). The aim of this study was to characterize the epitope regions of nine anti-NS1 human monoclonal Abs (HuMAbs) derived from six patients secondarily infected with DENV-2. These anti-NS1 HuMAbs were cross-reactive with DENV-1, -2, and -3 but not DENV-4. All HuMAbs bound a common epitope region located between amino acids 221 and 266 of NS1. This study is the first report to map a DENV-NS1 epitope region using anti-DENV MAbs derived from patients.
Background and objective
Human T‐cell lymphotropic viruses (HTLV) 1 and 2 are endemic in sub‐Saharan Africa (SSA), transfusion‐transmissible and causally linked to various severe diseases. However, even in SSA countries with moderate to high endemicity, routine blood donor screening for HTLV is rarely, if ever, performed. Information on seroprevalence is limited. The aim of this review is to establish the prevalence of HTLV‐1 and HTLV‐1/2 among blood donors in sub‐Saharan Africa.
Materials and Methods
We systematically reviewed databases including EMBASE, MEDLINE and the Cochrane database library from their inception to June 2018. Studies presenting data on HTLV prevalence among blood donors in sub‐Saharan Africa were included. A random‐effect meta‐analysis was conducted on all eligible studies.
Results
A total of 25 studies were included, representing 74 119 blood donors, of whom over 80% (61 002) were only tested for HTLV‐1. The evidence base was high and moderate in quality. The pooled prevalence of the 17 studies that screened only for HTLV‐1 and the nine studies that screened for HTLV‐1/2 was 0·68 (95% CI: 0·29–1·60) and 1·11 (95% CI: 0·47–2·59) per 100 blood donors, respectively.
Conclusion
The prevalence of HTLV‐1 infection among blood donors is relatively low. The current review is intended to inform debates and decisions about best practices to prevent transfusion‐transmitted HTLV in sub‐Saharan Africa. Further work is required to determine the risk of infections by transfusion and the cost‐effectiveness of any new measures such as routine screening.
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