Conference highlights of the 15th international conference on human retrovirology: HTLV and related retroviruses, 4-8 june 2011, Leuven, Gembloux, Belgium

The June 2011 15th International Conference on Human Retrovirology: HTLV and Related Viruses marks approximately 30 years since the discovery of HTLV-1. As anticipated, a large number of abstracts were submitted and presented by scientists, new and old to the field of retrovirology, from all five continents. The aim of this review is to distribute the scientific highlights of the presentations as analysed and represented by experts in specific fields of epidemiology, clinical research, immunology, animal models, molecular and cellular biology, and virology

Multiple recombinant events in human T-Cell leukemia virus type 1: complete sequences of recombinant African strains.

Africa is the largest known endemic area for HTLV-1, with a high diversity of molecular genotypes. We previously demonstrated that some HTLV-1 strains from North Africa (the a-NA clade) are the result of a recombinant event between Senegalese and West African strains. To better characterize these recombinants and their distribution, we sequenced the LTR region and/or a env gene fragment of a series of 52 HTLV-1 strains from 13 different countries in North and West Africa. Four samples from descendants of African slaves and native to French Guiana were also added. Furthermore, we characterized the complete sequence for 7 viral strains, from the different genotypes. Until now, no complete sequence was available for a-NA clade. Phylogenetic analysis demonstrates that most of the new African strains belong to the Cosmopolitan a-genotype. Ten new strains from the recombinant North African (a-NA) clade could be found in Morocco, Western Sahara, Mali, Guinea, Côte d'Ivoire, and Ghana. We also identified a new clade (named a-G-Rec) comprising 4 strains from Guinea and Ghana that arose from a distinct recombination event between strains from Senegal and West Africa. The analyses of complete sequences suggest that recombination does not only occur in the LTR but also in other regions (env/pol) of the genome. Our data strongly suggest that a-NA and a-G-Rec strains have a mosaic profile with genetic segments deriving from either a-WA or a-Sen strains. In conclusion, our work demonstrates that recombination in HTLV-1 may not be such a rare event as previously proposed

HIV-1 hijacks the cell extracellular matrix to spread collectively and efficiently between T lymphocytes

ABSTRACT Collective transmission via structures containing several virions has recently emerged as a highly efficient mode of viral spread. Here, we demonstrate that HIV-1 spreads between T lymphocytes in the form of viral particles colonies that are concentrated and sheltered in an extracellular matrix (ECM) lattice enabling their collective transmission upon cell contacts. Intrinsically, ECM-clustered viruses infect T lymphocytes more efficiently than individual viral particles. They preserve HIV-1 transmission from antiretroviral treatment (ArT) and potent broadly neutralizing antibodies. We also show that collagen induced by HIV-1 infection controls the clustering of virions and their collective spread, thereby enhancing infectivity. CD4+ T cells from HIV-1-infected patients produce and transmit ECM-virus clusters, supporting that they could be involved in vivo . This study provides new insights into modes of HIV-1 transmission and identifies a novel fundamental role for collagen in this process. HIV-1 spread via ECM-virus clusters may have important implications for viral dissemination and persistence, including during therapy

HTLV-1 Rex hijacks UPF1 in a CRM1 dependent manner, leading to NMD inhibition and revealing unexpected proviral roles of UPF1

Abstract The hijacking of CRM1 export is an important step of the retroviral replication cycle. Here, we investigated the consequences of this hijacking for the host. During HTLV-1 infection, we identified the formation of a complex composed of Rex, CRM1 and the RNA helicase UPF1, leading to the nuclear retention of UPF1. We further showed how this leads to the inhibition of the nonsense mediated mRNA decay (NMD), known to have an antiviral function. Corroborating these results, we described a similar process with Rev, the functional homolog of Rex from HIV-1. Unexpectedly, we also found that, for HTLV-1, this process is coupled with the specific loading of UPF1 onto vRNA, independently of NMD. In this latter context, UPF1 positively regulates several steps of the viral replication cycle, from the nuclear export of vRNA to the production of mature viral particles