High-level of viral genomic diversity in cervical cancers: a Brazilian study on human papillomavirus type 16

Invasive cervical cancer (ICC) is the third most frequent cancer among women worldwide and is associated with persistent infection by carcinogenic human papillomaviruses (HPVs). The combination of large populations of viral progeny and decades of sustained infection may allow for the generation of intra-patient diversity, in spite of the assumedly low mutation rates of PVs. While the natural history of chronic HPVs infections has been comprehensively described, within-host viral diversity remains largely unexplored. In this study we have applied next generation sequencing to the analysis of intra-host genetic diversity in ten ICC and one condyloma cases associated to single HPV16 infection. We retrieved from all cases near full-length genomic sequences. All samples analyzed contained polymorphic sites, ranging from 3 to 125 polymorphic positions per genome, and the median probability of a viral genome picked at random to be identical to the consensus sequence in the lesion was only 40%. We have also identified two independent putative duplication events in two samples, spanning the L2 and the L1 gene, respectively. Finally, we have identified with good support a chimera of human and viral DNA. We propose that viral diversity generated during HPVs chronic infection may be fueled by innate and adaptive immune pressures. Further research will be needed to understand the dynamics of viral DNA variability, differentially in benign and malignant lesions, as well as in tissues with differential intensity of immune surveillance. Finally, the impact of intralesion viral diversity on the long-term oncogenic potential may deserve closer attention.

The effect of high-fat diet on rat’s mood, feeding behavior and response to stress

An association between obesity and depression has been indicated in studies addressing common physical (metabolic) and psychological (anxiety, low self-esteem) outcomes. Of consideration in both obesity and depression are chronic mild stressors to which individuals are exposed to on a daily basis. However, the response to stress is remarkably variable depending on numerous factors, such as the physical health and the mental state at the time of exposure. Here a chronic mild stress (CMS) protocol was used to assess the effect of high-fat diet (HFD)-induced obesity on response to stress in a rat model. In addition to the development of metabolic complications, such as glucose intolerance, diet-induced obesity caused behavioral alterations. Specifically, animals fed on HFD displayed depressive- and anxious-like behaviors that were only present in the normal diet (ND) group upon exposure to CMS. Of notice, these mood impairments were not further aggravated when the HFD animals were exposed to CMS, which suggest a ceiling effect. Moreover, although there was a sudden drop of food consumption in the first 3 weeks of the CMS protocol in both ND and HFD groups, only the CMS-HFD displayed an overall noticeable decrease in total food intake during the 6 weeks of the CMS protocol. Altogether, the study suggests that HFD impacts on the response to CMS, which should be considered when addressing the consequences of obesity in behavior.