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Background & Aims: Despite high‐risk behaviour, 10%‐20% of HCV multiple exposed individuals remain uninfected (MEU), whilst the remainder become infected (MEI). We hypothesize that host factors play a role in HCV susceptibility. We aimed to identify polymorphisms in host genes that encode for proteins involved in viral entry: CD81, Scavenger receptor 1 (SR‐1), Low‐density lipoprotein receptor (LDL‐R), Claudin‐1 (CLDN1), Occludin (OCLN) and Niemann‐Pick C1–like 1 (NPC1L1). Methods: Multiple exposed infected and MEU from two observational cohorts were selected. From the MSM study of acute infection with HCV (MOSAIC), HIV‐1 infected MEU cases (n = 30) and HIV‐1 infected MEI controls (n = 32) were selected based on reported high‐risk behaviour. From the Amsterdam Cohorts Studies (ACS) injecting drug users (IDU) cohort, MEU cases (n = 40) and MEI controls (n = 22) were selected who injected drugs for ≥2 years, in the nineties, when HCV incidence was high. Selected single nucleotide polymorphisms (SNPs) were determined by sequencing or SNP assays. Results: No associations were found for SNPs within genes coding for CD81, SR‐1, Claudin‐1 or Occludin between the MEU and MEI individuals from either cohort. We did observe a significant association for rs688 within the LDL‐R gene with HCV infection (OR: 0.41 P = 0.001), however, LDL cholesterol levels did not vary between individuals carrying the differential SNPs. Additionally, a marginal significant effect was found for rs217434 and rs2072183 (OR: 2.07 P = 0.032 and OR: 1.76 P = 0.039, respectively) within NPC1L1. Conclusions: Our results demonstrate that the rs688 SNP within the LDL‐R gene associates with HCV susceptibility through mucosal as well as intravenous exposure. [ABSTRACT FROM AUTHOR]

Background Hepatitis B virus (HBV) is divided into 8 definite (A-H) and 2 putative (I, J) genotypes that show a geographical distribution. HBV genotype G, however, is an aberrant genotype of unknown origin that demonstrates severe replication deficiencies and very little genetic variation. It is often found in co-infections with another HBV genotype and infection has been associated with certain risk groups such as intravenous drug users and men having sex with men (MSM). We aimed to estimate the prevalence of HBV-G in the Netherlands by analysing samples from HBV-positive patients visiting the Academic Medical Center in Amsterdam. Methods Ninety-six HBV-infected patients, genotyped as HBV-A or HBV-G infected, were retrieved from the clinical database. Blood plasma samples were analysed with a newly-developed real-time PCR assay that detects HBV-A and HBV-G. For three patients, the HBV plasma viral load (pVL) of both genotypes was followed longitudinally. In addition, three complete genomes of HBV-G were sequenced to determine their relationship to global HBV-G strains. Results Ten HBV-G infections were found in the selected Dutch patients. All concerned HIV-1 infected males with HBV-A co-infection. Dutch HBV-G strains were phylogenetically closely related to reference HBV-G strains. Conclusions In this study, HBV-G infection in the Netherlands is found exclusively in HIV-1 infected men as co-infection with HBV-A. A considerable percentage (37%) of men infected with HBV and HIV-1 are actually co- infected with two HBV genotypes. [ABSTRACT FROM AUTHOR]

An HIV-1 diagnostic laboratory was established in the Academic Medical Center (AMC) of the University of Amsterdam after the discovery of human immunodeficiency virus (HIV) as the cause of the acquired immunodeficiency syndrome (AIDS). The first AIDS patients were diagnosed here in 1981 and since 1983 we have tested the samples of 50992 patients using a variety of assays that greatly improved over the years. We will describe some of the basic results from this diagnostic laboratory and then focus on the spin-off in terms of the development of novel virus assays to detect super-infections and ultra-sensitive assays to measure the intracellular HIV-1 RNA load. We also review several original research findings in the field of HIV-1 virology that stem from initial observations made in the diagnostic unit. This includes the study of genetic defects in the HIV-1 genome and time trends of the replication fitness over 30 years of viral evolution, but also the description of novel HIV-1 variants in difficult-to-diagnose clinical specimen. [ABSTRACT FROM AUTHOR]

Abstract: Two antiviral approaches against the human immunodeficiency virus type 1 (HIV-1) were presented at the Antivirals Congress in Amsterdam. The common theme among these two separate therapeutic research lines is the wish to develop a durable therapy that prevents viral escape. We will present a brief overview of these two research lines and focus on our efforts to design an escape-proof anti-HIV therapy. The first topic concerns the class of HIV-1 fusion inhibitors, including the prototype T20 peptide and the improved versions T1249 and T2635, which were all developed by Trimeris–Roche. The selection of T20-resistant HIV-1 strains is a fairly easy evolutionary process that requires a single amino acid substitution in the peptide binding site of the viral envelope glycoprotein (Env) target. The selection of T1249-resistant HIV-1 strains was shown to require a more dramatic amino acid substitution in the viral Env protein, in particular the introduction of charged amino acid residues that cause resistance by charge-repulsion of the antiviral peptide. The third generation peptide T2635 remains active against all these HIV-1 escape variants because the charged residues within this peptide are “masked” by an introduced intra-helical salt bridge. This charge masking concept could facilitate the future design of escape-proof antiviral peptides. The second topic concerns the mechanism of RNA interference (RNAi) that we are currently employing to develop an antiviral gene therapy. One can make human T cells resistant to HIV-1 infection by a stable RNAi-inducing gene transfer, but the virus escapes under therapeutic pressure of a single inhibitor. Several options for a combinatorial RNAi attack to prevent viral escape will be discussed. The simultaneous use of multiple RNAi inhibitors turns out to be the most effective and durable strategy. [Copyright &y& Elsevier]

Retroviruses and LTR-retrotransposons are widespread in all living organisms and, in some instances such as for HIV, can be a serious threat to the human health. The retroviral nucleocapsid is the inner structure of the virus where several hundred nucleocapsid protein (NC) molecules coat the dimeric, genomic RNA. During the past twenty years, NC was found to play multiple roles in the viral life cycle (Fig. 1), notably during the copying of the genomic RNA into the proviral DNA by viral reverse transcriptase and integrase, and is therefore considered to be a prime target for anti-HIV therapy. The 6th NC symposium was held in the beautiful city of Amsterdam, the Netherlands, on the 20th and 21st of September 2007. All aspects of NC biology, from structure to function and to anti-HIV vaccination, were covered during this meeting. [ABSTRACT FROM AUTHOR]

A pol-fragment of simian immunodeficiency virus (SIV) that is highly related to SIVdr1-pol from drill monkeys (Mandrillus leucophaeus) was detected in two mandrills (Mandrillus sphinx) from Amsterdam Zoo. These captivity-born mandrills had never been in contact with drill monkeys, and were unlikely to be hybrids. Their mitochondrial haplotype suggested that they descended from founder animals in Cameroon or northern Gabon, close to the habitat of the drill. SIVdr1 has once before been found in a wild-caught mandrill from the same region, indicating that mandrills are naturally infected with a SIVdr1-like virus. This suggests that mandrills are the first primate species to be infected with three strains of SIV: SIVmnd1, SIVmnd2, and SIVdr1. [ABSTRACT FROM AUTHOR]