It's the virus, stupid – part 2

This editorial presents Retrovirology's choice for the best basic science "retrovirus paper of the year 2005"

HIV-1 drug-resistance and drug-dependence

In this review, we will describe several recent HIV-1 studies in which a drug-dependent virus variant was selected. A common evolutionary route to the drug-dependence phenotype is proposed. First, the selection of a drug-resistance mutation that also affects the function of the targeted viral protein. Second, a compensatory mutation that repairs the protein function, but in the presence of the drug, which becomes an intrinsic part of the mechanism. The clinical relevance of drug-dependent HIV-1 variants is also discussed

Jan van der Noordaa (1934-2015); A Virologist Pur Sang.

Our loyal friend and colleague, Jan van der Noordaa, passed away unexpectedly at the age of 80 on the evening of 17 June 2015. [...

A novel approach for inhibition of HIV-1 by RNA interference: counteracting viral escape with a second generation of siRNAs

RNA interference (RNAi) is an evolutionary conserved gene silencing mechanism in which small interfering RNA (siRNA) mediates the sequence specific degradation of mRNA. The recent discovery that exogenously delivered siRNA can trigger RNAi in mammalian cells raises the possibility to use this technology as a therapeutic tool against pathogenic viruses. Indeed, it has been shown that siRNAs can be used effectively to inhibit virus replication. The focus of this review is on RNA interference strategies against HIV-1 and how this new technology may be developed into a new successful therapy. One of the hallmarks of RNAi, its sequence specificity, also presents a way out for the virus, as single nucleotide substitutions in the target region can abolish the suppression. Strategies to prevent the emergence of resistant viruses have been suggested and involve the targeting of conserved sequences and the simultaneous use of multiple siRNAs, similar to current highly active antiretroviral therapy. We present an additional strategy aimed at preventing viral escape by using a second generation of siRNAs that recognize the mutated target sites

2008 Nobel prize in Medicine for discoverers of HIV

Françoise Barré-Sinoussi and Luc Montagnier, codiscoverers of HIV, the causative agent of AIDS, have been awarded the 2008 Nobel Prize in Physiology or Medicine. They share this prize with Harald zur Hausen who was responsible for establishing the link between human papilloma virus infection and cervical carcinoma

The First Strand Transfer during HIV-1 Reverse Transcription Can Occur either Intramolecularly or Intermolecularly

AbstractReverse transcription is a complicated process that involves at least two cDNA transfer reactions to produce a full-length copy DNA of the retroviral RNA genome. Because one retrovirus particle contains two identical genomic RNA molecules, the transfers can occur in an intramolecular or intermolecular manner. The mechanism of the first transfer step (minus-strand strong-stop cDNA transfer) has been studied previously in detail in transduction experiments with spleen necrosis virus vectors containing genetic markers. Different results have been reported with respect to the type of strand transfer mechanism. In this study, we analyzed the first strand transfer for human immunodeficiency virus type 1 (HIV-1). Two genetically marked genomes were copackaged into virions and reverse transcription was initiated within these particles upon permeabilization by NP-40 and addition of dNTPs. To test whether intrastrand or interstrand transfer had occurred, the cDNA products of this endogenous reverse transcription reaction were extracted from the virions and analyzed for the presence of restriction enzyme recognition sites provided by the genetic markers. The results of this analysis demonstrated that the first DNA transfer reaction occurs in a random manner, with approximately the same contribution of intrastrand and interstrand transfers. The ability to perform intermolecular strand transfer was lost upon extraction of the dimeric RNA template from the virion particle