Conclude that this must largely be due to changes in higher collagen structures. Collectively these findings add considerable precision to the very general clinical observation that connective tissue mechanical properties change with age and diabetes. These findings also sharpen focus on the range of possible vectors by which AGE accumulation in collagen tissue is likely to affect tissue homeostasis and drive tissue pathology. Homologous recombination is increasingly recognized as a major mechanism for maintaining genetic diversity of viruses. In fact, phylogenetic analyses of clinical herpes simplex virus 1 isolates have shown that homologous recombination occurs frequently and that this mechanism seems to be essential for HSV1 evolution, and for maintaining genomic integrity Similar observations have also been made for other alphaherpesviruses. Homologous recombination is also responsible for genomic isomerization occurring during HSV-1 replication. The HSV-1 genome consists of two segments, designated unique long and unique short. Each segment is flanked by inverted repeats containing a variable number of the a sequence. The a sequences are sites for cleavage of concatemeric genomes into monomers, which will be packaged into virus particles. During an infection a mixed population of genomes, in which the UL and US segments exist in four different orientations, is created. The genome isomers are found in equimolar ratios, reflecting a high Paclitaxel Microtubule inhibitor frequency of homologous recombination. The importance of homologous recombination for HSV-1 to acquire genetic segments required for virulence has been demonstrated in animal models. Moreover, in vivo studies have shown high recombination rates between animal herpesviruses. After a primary infection of epithelial cells, HSV-1 establishes latency in sensory ganglia and intermittently reactivates, causing oral lesions. More commonly, however, the virus reactivates without symptoms i.e. asymptomatic shedding of virus. Several studies have shown that the same individual can be infected by different HSV-1 strains and that both original and recombinant strains can be reactivated. As the HSV-1 infection is common, with a high prevalence worldwide, it is likely that different HSV-1 strains can replicate simultaneously in the same epithelial or nerve cell, making recombination between strains possible. Homologous recombination is greatly enhanced by doublestrand breaks in DNA, which can be repaired in an error-free manner employing Rad51, ensuring high-fidelity base-pairing between complementary strands. During an HSV-1 infection homologous recombination may be initiated in several ways. Cleavage and processing of repeated a sequences take place between the inverted repeats of UL and US segments, and may initiate homologous recombination, resulting in four possible isomers of the bi-partite genome.