XMRV as a Human Pathogen?

Xenotropic murine leukemia virus-related virus (XMRV) has been proposed to be associated with prostate cancer and chronic fatigue syndrome (CFS). This proposition has been controversial because many investigators have failed to replicate the reported associations. Here, we explore whether XMRV is an authentic human pathogen in the light of recent findings that indicate otherwise

The Retrovirology Open Access experience

The Retrovirology Open Access experience after publishing more than 500 articles is discussed

From Duke to King's: Michael Malim wins the 2010 Retrovirology prize

Michael H. Malim wins the Retrovirology prize

The 2011 Retrovirology Prize winner Masao Matsuoka: forward looking and antisense

Masao Matsuoka wins the 2011 Retrovirology Prize

Current On-Line Issues

With the frenetic pace of technological development in the area of global communications, it is no wonder that consumers and businesses are adopting and taking advantage of these technologies before they are fully mature. The law is being refined every day. Most recently, the Supreme Court granted certiorari to decide whether Congress\u27s recent twenty-year extension of the term of copyright protection is constitutional. Hotly disputed topics include digital copyright and liability for trademark infringement from technologically-driven issues such as hyperlinking and metatag use. This move to the Internet, to our client\u27s surprise, presented a variety of legal issues that must be dealt with. For example, who owns the data pertinent to these tenants? How does our client keep its server data secure? Who owns the copyrights and trademarks that will be used during the on-line sessions? After our client\u27s initial foray into the U.S. market, what international issues arise when our client begins to service customers in the European Union or other countries? A closer inspection reveals that, with planning, our clients may embrace this move, because any lurking dangers may be avoided

Endogenous Retroviruses: Thierry Heidmann wins the 2009 Retrovirology prize

Thierry Heidmann wins the 2009 Retrovirology prize

A peptide-loaded dendritic cell based cytotoxic T-lymphocyte (CTL) vaccination strategy using peptides that span SIV Tat, Rev, and Env overlapping reading frames

CTL based vaccine strategies in the macaque model of AIDS have shown promise in slowing the progression to disease. However, rapid CTL escape viruses can emerge rendering such vaccination useless. We hypothesized that such escape is made more difficult if the immunizing CTL epitope falls within a region of the virus that has a high density of overlapping reading frames which encode several viral proteins. To test this hypothesis, we immunized macaques using a peptide-loaded dendritic cell approach employing epitopes in the second coding exon of SIV Tat which spans reading frames for both Env and Rev. We report here that autologous dendritic cells, loaded with SIV peptides from Tat, Rev, and Env, induced a distinct cellular immune response measurable ex vivo. However, conclusive in vivo control of a challenge inoculation of SIVmac239 was not observed suggesting that CTL epitopes within densely overlapping reading frames are also subject to escape mutations

Ago-2-Mediated Slicer Activity Is Essential for Anti-Flaviviral Efficacy of RNAi

RNA interference can be mediated by fully complementary siRNA or partially complementary miRNA. siRNAs are widely used to suppress viral replication and the fully complementary siRNA bound Ago-2 in the RISC is known to degrade the target RNA. Although other argonaute proteins lacking slicer activity can also bind oligonucleotides with both si and miRNA structures, whether they can also contribute to antiviral effects is not entirely clear. We tested si and miRNA structured oligos for target repression in dual luciferase assays as well as for inhibition of Dengue and West Nile virus replication in ES cells expressing individual Ago proteins. In luciferase assays, both fully complementary and partially complementary oligos effectively repressed their targets in all individual Ago expressing cell lines, although the efficacy with fully complementary oligos was higher in Ago-2+ cells. However, partially complementary oligos had no effect on virus replication in any cell line, while fully complementary siRNAs were highly effective in Ago-2 expressing, but not in cells expressing other Ago proteins. This occurred irrespective of whether the target sequences were located in the coding region or 3′UTR of the virus. We conclude that Ago-2 slicer activity is essential for anti-viral efficacy of siRNAs and miRNA-mediated translational repression/transcript destabilization is too weak to suppress the abundantly expressed flaviviral proteins

Increased production of viral proteins by a 3'-LTR-deleted infectious clone of human T-cell leukemia virus type 1

We previously reported that a full-length provirus of HTLV-1 was directly constructed from the HTLV-1-transformed cell line MT-2 using overlapping polymerase chain reaction (PCR) and cloned into a plasmid vector (pFL-MT2). 293T cells transfected with pFL-MT2 alone did not produce virus particles because there was no expression of the viral transactivator protein Tax, whereas cells transfected with pFL-MT2 plus a Tax expression vector produced virus-like particles. In the process of constructing the HTLV-1 provirus by overlapping PCR, we also constructed an incomplete molecular clone, in which the 3' long terminal repeat (LTR) was replaced with the endogenous human gene, which resulted in the expression of a tax gene shorter by 43 bp. This incomplete molecular clone alone expressed Tax and produced the viral protein in transfected cells. Various clones were then constructed with different lengths of the 3' LTR and lacking the reverse-direction TATA box. The clones contained over 113 bp of the 3' LTR, with no reverse-direction TATA box, which might express the full-length tax gene, and did not produce the viral antigen. These results suggest that Tax in which the C-terminal portion is deleted is more strongly expressed than the wild-type protein and has transcriptional activity