The persistence of H5N1 avian influenza viruses in many Asian countries and their ability to cause fatal infections in humans have raised serious concerns about a global flu pandemic. Here we report the isolation of an H5N1 virus from a Vietnamese girl that is resistant to the drug oseltamivir, which is an inhibitor of the viral enzyme neuraminidase and is currently used for protection against and treatment of influenza. Further investigation is necessary to determine the prevalence of oseltamivir-resistant H5N1 viruses among patients treated with this drug.

Background: The mononegavirus superfamily (Mononegavirales) comprises three families, Rhabdoviridae, Paramyxoviridae and Filoviridae. These viruses possess a single stranded negative sense RNA as the genome. Recentsuccessintherecoveryofinfectiousvirusfroma transfected cDNA of mononegaviruses including Sendai virus, a prototypic paramyxovirus, is opening the possibility of their genetic engineering. However, infectious viruses have been recovered only by initiating the infectious cycle with cDNA directing the synthesis of antigenomic positive sense ( ) RNA. Starting with genomic negative sense (ÿ) RNA has been unsuccessful. Furthermore, the recovery efficiency has often been extremely low.

Mononegavirus gene expression is generally monocis-2 Corresponding author tronic, each mRNA usually directing a single primary translation product. However, the P gene of the subfamily The Sendai virus (SeV) V protein is characterized by Paramyxovirinae in the Paramyxoviridae is a notable the unique cysteine-rich domain in its carboxy-terminal exception, because it gives rise to multiple protein species half which is fused to the amino-terminal half of the by means of overlapping frames and by a remarkable P protein, but its function has remained enigmatic.process known as RNA editing or pseudotemplated addiThe V protein-directing mRNA is generated by a tion of nucleotides (for review, see Lamb and Kolakofsky, remarkable process known as mRNA editing involving 1996). The P gene is the second proximal to the 3Ј-terminus the pseudotemplated addition of a single G residue at in these viruses. RNA editing to insert pseudotemplated G a specific septinucleotide locus in the P gene, whereas residues is found for all the three paramyxovirus genera. the unedited exact copy encodes the P protein. Here, It is a virus-specific event which takes place co-transcripwe introduced two nucleotide changes in the septitionally by reiterative copying of the short C stretch at a nucleotide motif (UUUUCCC to UUCUUCC) in a fullspecific region on the genome template (Vidal et al., length SeV cDNA and were able to recover a virus 1990a). The septinucleotide consensus motif (3Ј-UUU/ from the cDNA, which was devoid of mRNA editing CUCCC-5Ј) including the C stretch has been proposed to and hence unable to synthesize the V protein. Combe a requirement for editing (Park and Krystal, 1992). A pared with the parental wild-type virus with regard to 'stuttering' model proposes that the polymerase pauses at gene expression, replication and cytopathogenicity in this site and, when the pause is sufficiently long, slippage various cell lines in vitro, the V(-) virus was found of the nascent mRNA occurs by one or two nucleotides, to be either potentiated or comparable but never thereby reiteratively inserting one or two Gs (Thomas attenuated. The V(-) virus, however, showed markedly et al., 1988;Vidal et al., 1990b). For Sendai virus (SeV) attenuated in vivo replication capacity in and patho- (Figure 1), bovine parainfluenza virus type 3 (genus genicity for mice. Thus, though categorized as a nonParamyxovirus) and measles virus (Morbillivirus), the essential gene product, SeV V protein encodes a luxury unedited mRNA that is the exact copy of the P gene function required for in vivo pathogenicity.encodes the P (phospho) protein, while the addition of Keywords: mRNA editing/pathogenicity/reverse genetics/ one G residue produces an mRNA that encodes the V Sendai virus/V(-) mutant protein (Vidal et al., 1990a;Galinski et al., 1992). The edited version (with insertion of one or two G residues) encodes the P protein and the unedited version the V protein for the genus Rubulavirus including SV5 (Thomas

CD26 is a leukocyte-activation antigen that is expressed on T lymphocytes and macrophages and possesses dipeptidyl peptidase IV (DPPIV) activity, whose natural substrates have not been identified yet. CXC chemokines, stromal cell-derived factor 1␣ (SDF-1␣) and 1␤ (SDF-1␤), sharing the receptor CXCR-4, are highly efficacious chemoattractants for resting lymphocytes and CD34 ؉ progenitor cells, and they efficiently block the CXCR-4-mediated entry into cells of T cell line tropic strains of HIV type 1 (HIV-1). Here we show that both the chemotactic and antiviral activities of these chemokines are abrogated by DPPIV-mediated specific removal of the N-terminal dipeptide, not only when the chemokines are produced in transformed mouse L cell line to express human CD26 but also when they were exposed to a human T cell line (H9) physiologically expressing CD26. Mutagenesis of SDF-1␣ confirmed the critical requirement of the N-terminal dipeptide for its chemotactic and antiviral activities. These data suggest that CD26-mediated cleavage of SDF-1␣ and SDF-1␤ likely occurs in human bodies and promotes HIV-1 replication and disease progression. They may also explain why memory function of CD4 ؉ cells is preferentially lost in HIV-1 infection. Furthermore, CD26 would modulate various other biological processes in which SDF-1␣ and SDF-1␤ are involved.