No abstract

Human enteroviruses consist of more than 60 serotypes, reflecting a wide range of evolutionary divergence. They have been genetically classified into four clusters on the basis of sequence homology in the coding region of the single-stranded RNA genome. To explore further the genetic relationships between human enteroviruses and to characterize the evolutionary mechanisms responsible for variation, previously sequenced genomes were subjected to detailed comparison. Bootstrap and genetic similarity analyses were used to systematically scan the alignments of complete genomic sequences. Bootstrap analysis provided evidence from an early recombination event at the junction of the 5′ noncoding and coding regions of the progenitors of the current clusters. Analysis within the genetic clusters indicated that enterovirus prototype strains include intraspecies recombinants. Recombination breakpoints were detected in all genomic regions except the capsid protein coding region. Our results suggest that recombination is a significant and relatively frequent mechanism in the evolution of enterovirus genomes.

Human immunodeficiency virus type 1 isolates of envelope genotype E are contributing substantially to the global pandemic. These strains appear to be mosaics, with the gag gene from clade A and the envelope from clade E; the parental clade E strain has not been found. Here we report the first full genomic sequence of one such mosaic virus, isolate CM240 from Thailand. Multiple breakpoints between the two parental genotypes have been found in a CM240 virus. The entire gag-pol region and most, if not all, of the accessory genes vif, vpr, tat, rev, and vpu appear to derive from clade A. The genotype switches to E shortly after the signal peptide of the envelope and back to clade A near the middle of gp41; thus, the portion of the envelope that lies on the cytoplasmic side of the membrane appears to be principally derived not from clade E, as previously thought, but from clade A. Another small segment not belonging to any recognized clade and presumably also contributed by the parental E strain has been found in the long terminal repeat. It may be significant that the implied virion structure resembles a pseudotype virus with the matrix and core from one clade and the outer envelope from another. In the long terminal repeat, differences were observed between CM240 and other clades in the number of NF-B binding sites, the sequence of the TATA box, and the putative secondary structure of the transactivation response region stem-loop. The mosaic structure of a CM240 virion is suggestive of phenotypic differences which might have contributed to the emergence of this variant.

BackgroundGlobal HIV-1 genetic diversity and evolution form a major challenge to treatment and prevention efforts. An increasing number of distinct HIV-1 recombinants have been identifiedworldwide, but their contribution to the global epidemic is unknown. We aimed to estimate the global and regional distribution of HIV-1 recombinant forms during 1990-2015. MethodsWe assembled a global HIV-1 molecular epidemiology database through a systematic literature review and a global survey. We searched PubMed, EMBASE (Ovid), CINAHL (Ebscohost), and Global Health (Ovid) for HIV-1 subtyping studies published from Jan 1, 1990, to Dec 31, 2015. Unpublished original HIV-1 subtyping data was collected through a survey among experts in the field who were members of the WHO-UNAIDS Network for HIV Isolation and Characterisation. We included prevalence studies with HIV-1 subtyping data collected during 1990-2015. Countries were grouped into 14 regions and analyses conducted for four time periods (1990-99, 2000-04, 2005-09 and 2010-15). The distribution of circulating recombinant forms (CRFs), and unique recombinant forms (URFs) in individual countries was weighted according to the UNAIDS estimates of the number of people living with HIV in each country to generate regional and global estimates of numbers and proportions of HIV-1 recombinants in each time period. The systematic review is registered with PROSPERO, number CRD42017067164.

The extraordinary genetic diversity of human immunodeficiency virus type 1 (HIV-1) results from the introduction of mutations by an error-prone reverse transcriptase and from recombination of the two RNA genomes packaged in the virion during the synthesis of proviral DNA. The occurrence of multiple, genetically distant HIV-1 subtypes and their geographic intermixing set up conditions for dramatic, rather than gradual, changes in genotype whenever genomes from different subtypes are copackaged in virions. Here we describe, for the first time, the sequential generation of multiple different, but related, intersubtype HIV-1 recombinants within an infected individual. Full-length gag and env genes were recovered directly from peripheral blood mononuclear cells or from primary virus cultures, using serial blood samples from a Zambian woman and a sample from her spouse. DNA sequencing and phylogenetic analysis established that two different A/C recombinant forms of HIV-1 predominated at two time points in the woman. A related but distinct recombinant HIV-1 was recovered from her spouse. Intersubtype recombination apparently played a central role in the evolution of HIV-1 in this couple and may contribute substantially to the rapid emergence of HIV-1 variants whenever mixed-subtype HIV-1 infections occur.