Actinic keratosis is no laughing matter – untreated, up to 20% of cases may pregress to skin cancer. At the same time, if this paper had been published on 1st April (it wasn’t) I would have had my doubts. I’ve seen some interesting virus sampling protocols in my time (bear in mind we sequenced the horse faeces virome), but this one is pretty unique. As a side benefit, also reduces the risk of monobrow.
Eyebrow hairs from actinic keratosis patients harbor the highest number of cutaneous human papillomaviruses. BMC Infectious Diseases 2013, 13: 186 doi:10.1186/1471-2334-13-186
Cutaneous human papillomavirus (HPV) infections seem to be associated with the onset of actinic keratosis (AK). This study compares the presence of cutaneous HPV types in eyebrow hairs to those in tissues of normal skin and skin lesions of 75 immunocompetent AK patients. Biopsies from AK lesions, normal skin and plucked eyebrow hairs were collected from each patient. DNA from these specimens was tested for the presence of 28 cutaneous HPV (betaPV and gammaPV) by a PCR based method. The highest number of HPV prevalence was detected in 84% of the eyebrow hairs (63/75, median 6 types) compared to 47% of AK lesions (35/75, median 3 types) (p< 0.001) and 37% of normal skin (28/75, median 4 types) (p< 0.001), respectively. A total of 228 HPV infections were found in eyebrow hairs compared to only 92 HPV infections in AK and 69 in normal skin. In all three specimens HPV20, HPV23 and/or HPV37 were the most prevalent types. The highest number of multiple types of HPV positive specimens was found in 76% of the eyebrow hairs compared to 60% in AK and 57% in normal skin. The concordance of at least one HPV type in virus positive specimens was 81% (three specimens) and 88-93% of all three combinations with two specimens. Thus, eyebrow hairs revealed the highest number of cutaneous HPV infections, are easy to collect and are an appropriate screening tool in order to identify a possible association of HPV and AK.
Since their discovery in 1971, the polyomaviruses JC (JCPyV) and BK (BKPyV), isolated from patients with progressive multifocal leukoencephalopathy and polyomavirus-associated nephropathy, respectively, remained for decades as the only known members of the Polyomaviridae family of viruses of human origin. Over the past five years, the application of new genomic amplification technologies has facilitated the discovery of several novel human polyomaviruses (HPyVs), bringing the present number to 10. These HPyVs share many fundamental features in common such as genome size and organization. Infection by all HPyVs is widespread in the human population, but they show important differences in their tissue tropism and association with disease. Much remains unknown about these new viruses.
This review discusses the problems associated with studying HPyVs, such as the lack of culture systems for the new viruses and the gaps in our basic understanding of their biology, and summarizes what is known so far about their distribution, life cycle, tissue tropism, their associated pathologies (if any), and future research directions. The Rapidly Expanding Family of Human Polyomaviruses: Recent Developments in Understanding Their Life Cycle and Role in Human Pathology. (2013) PLoS Pathog 9(3): e1003206. doi:10.1371/journal.ppat.1003206
Until a few years ago the polyomavirus family (Polyomaviridae) included a dozen viruses identified in avian and mammal hosts. Two of these, the JC and BK-polyomaviruses isolated long time ago, are known to infect humans and cause severe illness in immunocompromized hosts. Since 2007 an unprecedented number of eight new polyomaviruses was discovered in humans. Among them are the KI and WU-polyomaviruses identified in respiratory samples, the Merkel cell polyomavirus found in skin carcinomas, and the polyomavirus associated with trichodysplasia spinulosa, a skin disease of transplant patients. Another four new human polyomaviruses were identified, HPyV6, HPyV7, HPyV9, and the Malawi polyomavirus, so far not associated with any disease. In the same period several new mammal polyomaviruses were described.
This review summarizes the recent developments in studying the new human polyomaviruses, and touches upon several aspects of polyomavirus virology, pathogenicity, epidemiology and phylogeny. From Stockholm to Malawi: recent developments in studying human polyomaviruses. J Gen Virol. 19 Dec 2012
Exactly how hepatitis B virus causes liver cancer has been a mystery for a long time. It is clear that the X protein (HBx) has something to do with it, but exactly what mechanisms are involved? These are very different to other cancer-causing viruses.
Some recent studies have demonstrated that viruses alter the expression of microRNAs, non-coding RNA molecules that can block the expression of target genes. Researchers have just reported that miR-148a is repressed by HBx to promote growth and metastasis of liver cancer. In normal liver cells, miR-148a represses the expression of the oncogenic protein HPIP, but the hepatitis B virus prevents expression of miR-148a, leading to increased levels of HPIP and subsequent oncogenic transformation. This study demonstrates that a cancer-associated virus promotes carcinogenesis through direct manipulation of a microRNA.
Hepatitis B virus X protein represses miRNA-148a to enhance tumorigenesis:http://goo.gl/2HkK7
Abstract: MicroRNAs (miRNAs) have been shown to be dysregulated in virus-related cancers; however, miRNA regulation of virus-related cancer development and progression remains poorly understood. Here, we report that miR-148a is repressed by hepatitis B virus (HBV) X protein (HBx) to promote cancer growth and metastasis in a mouse model of hepatocellular carcinoma (HCC). Hematopoietic pre–B cell leukemia transcription factor–interacting protein (HPIP) is an important regulator of cancer cell growth. We used miRNA target prediction programs to identify miR-148a as a regulator of HPIP. Expression of miR-148a in hepatoma cells reduced HPIP expression, leading to repression of AKT and ERK and subsequent inhibition of mTOR through the AKT/ERK/FOXO4/ATF5 pathway. HBx has been shown to play a critical role in the molecular pathogenesis of HBV-related HCC. We found that HBx suppressed p53-mediated activation of miR-148a. Moreover, expression of miR-148a was downregulated in patients with HBV-related liver cancer and negatively correlated with HPIP, which was upregulated in patients with liver cancer. In cultured cells and a mouse xenograft model, miR-148a reduced the growth, epithelial-to-mesenchymal transition, invasion, and metastasis of HBx-expressing hepatocarcinoma cells through inhibition of HPIP-mediated mTOR signaling. Thus, miR-148a activation or HPIP inhibition may be a useful strategy for cancer treatment.
Nature has just published an excellent supplement (free full access) on human papillomavirus. The new material is medical rather than biological in slant, covering vaccination and diagnostic tests rather than the basic biology of HPV, but still well worth a look:
Researchers have published the first annotated atlas of the Epstein-Barr virus genome, creating the most comprehensive study of how the virus genome interacts with its human host during a latent infection. Epstein-Barr virus (EBV), which is thought to be responsible for one percent of all human cancers, establishes a latent infection in nearly 100 percent of infected adult humans. The atlas is designed to guide researchers toward new means of creating therapies against EBV-latent infection and the cancers associated with latent EBV infection, such as B cell lymphomas, gastric carcinomas, and nasopharyngeal carcinomas. The project provides the best look yet at how EBV interacts with the genes and proteins of its host cells.A representation of the annotated EBV “epigenome,” listing the protein and chemical decorations added to the EBV DNA that get passed along to new copies of the EBV virus. As a supplement to the EBV genome—the characterization of the virus’s genes—the atlas describes the epigenome—all the protein and chemical decorations added to the EBV DNA that get passed along to new copies of the EBV virus–and the transcriptome—the catalog of all the RNA transcripts created from EBV DNA, which are either coded into protein or serve to regulate DNA directly. The researchers discovered numerous new points of interaction between viral DNA and its host, highlighting the extensive coevolution of the virus and pointing toward possible targets for future cancer and anti-viral drugs. (Eurekalert)
An atlas of the epstein-barr virus transcriptome and epigenome reveals host-virus regulatory interactions. Cell Host Microbe. 16 Aug 2012, 12(2):233-245
Epstein-Barr virus (EBV), which is associated with multiple human tumors, persists as a minichromosome in the nucleus of B lymphocytes and induces malignancies through incompletely understood mechanisms. Here, we present a large-scale functional genomic analysis of EBV. Our experimentally generated nucleosome positioning maps and viral protein binding data were integrated with over 700 publicly available high-throughput sequencing data sets for human lymphoblastoid cell lines mapped to the EBV genome. We found that viral lytic genes are coexpressed with cellular cancer-associated pathways, suggesting that the lytic cycle may play an unexpected role in virus-mediated oncogenesis. Host regulators of viral oncogene expression and chromosome structure were identified and validated, revealing a role for the B cell-specific protein Pax5 in viral gene regulation and the cohesin complex in regulating higher order chromatin structure. Our findings provide a deeper understanding of latent viral persistence in oncogenesis and establish a valuable viral genomics resource for future exploration.
Although studies have so far failed to find an infectious agent, the evidence is now pretty clear that “professional exposure to goats” increases the risk of lung cancer.
Professional Exposure to Goats Increases the Risk of Pneumonic-Type Lung Adenocarcinoma: Results of the IFCT-0504-Epidemio Study. (2012) PLoS ONE 7(5): e37889. doi:10.1371/journal.pone.0037889
Pneumonic-type lung adenocarcinoma (P-ADC) represents a distinct subset of lung cancer with specific clinical, radiological, and pathological features. Given the weak association with tobacco-smoking and the striking similarities with jaagsiekte sheep retrovirus (JSRV)-induced ovine pulmonary adenocarcinoma, it has been suggested that a zoonotic viral agent infecting pulmonary cells may predispose to P-ADC in humans. Our objective was to explore whether exposure to domestic small ruminants may represent a risk factor for P-ADC. We performed a multicenter case-control study recruiting patients with P-ADC as cases and patients with non-P-ADC non-small cell lung cancer as controls. A dedicated 356-item questionnaire was built to evaluate exposure to livestock. A total of 44 cases and 132 controls were included. At multivariate analysis, P-ADC was significantly more associated with female gender (Odds-ratio (OR) = 3.23, 95% confidence interval (CI): 1.32–7.87, p = 0.010), never- smoker status (OR = 3.57, 95% CI: 1.27–10.00, p = 0.015), personal history of extra-thoracic cancer before P-ADC diagnosis (OR = 3.43, 95% CI: 1.10–10.72, p = 0.034), and professional exposure to goats (OR = 5.09, 95% CI: 1.05–24.69, p = 0.043), as compared to other subtypes of lung cancer. This case-control suggests a link between professional exposure to goats and P-ADC, and prompts for further epidemiological evaluation of potential environmental risk factors for P-ADC.
Helicobacter pylori is a spiral-shaped, flagellated, microaerophilic Gram-negative bacillus discovered at the beginning of the 1980s that causes gastritis, peptic ulcers and stomach cancer in humans. So what’s new?
Helicobacter pylori infection: what’s new. Current Opinion in Infectious Diseases, 25(3): 337–344 Helicobacter pylori colonizes the human stomach causing gastritis and severe diseases including gastric cancer. One of the most dangerous H. pylori factors, CagA, has been investigated in relation to gastric cancer: recently this relationship was strongly reinforced by the finding that CagA interacts with the tumor suppressor apoptosis-stimulating protein of p53-2 (ASPP2), promoting p53 degradation. Treg have been proposed to be involved in H. pylori infection and gastric disease: recent findings suggest that Treg-induced tolerance, rather than immunity to H. pylori, may result in less severe disease. The eradication rates achieved with the standard triple therapy dropped below 80%, mainly due to antibiotic resistance, while no vaccines are currently licensed; new treatments/regimens were subjected to clinical trials, in some cases strongly increasing the eradication rates.
One in six cancers – two million a year globally – are caused by largely treatable or preventable infections. Makes you think, doesn’t it?
Global burden of cancers attributable to infections in 2008: a review and synthetic analysis. The Lancet Oncology, 9 May 2012, doi:10.1016/S1470-2045(12)70137-7
Background: Infections with certain viruses, bacteria, and parasites have been identified as strong risk factors for specific cancers. An update of their respective contribution to the global burden of cancer is warranted.
Methods: We considered infectious agents classified as carcinogenic to humans by the International Agency for Research on Cancer. We calculated their population attributable fraction worldwide and in eight geographical regions, using statistics on estimated cancer incidence in 2008. When associations were very strong, calculations were based on the prevalence of infection in cancer cases rather than in the general population. Estimates of infection prevalence and relative risk were extracted from published data.
Findings: Of the 12·7 million new cancer cases that occurred in 2008, the population attributable fraction (PAF) for infectious agents was 16·1%, meaning that around 2 million new cancer cases were attributable to infections. This fraction was higher in less developed countries (22·9%) than in more developed countries (7·4%), and varied from 3·3% in Australia and New Zealand to 32·7% in sub-Saharan Africa. Helicobacter pylori, hepatitis B and C viruses, and human papillomaviruses were responsible for 1·9 million cases, mainly gastric, liver, and cervix uteri cancers. In women, cervix uteri cancer accounted for about half of the infection-related burden of cancer; in men, liver and gastric cancers accounted for more than 80%. Around 30% of infection-attributable cases occur in people younger than 50 years.
Interpretation: Around 2 million cancer cases each year are caused by infectious agents. Application of existing public health methods for infection prevention, such as vaccination, safer injection practice, or antimicrobial treatments, could have a substantial effect on the future burden of cancer worldwide.
Yuan Chang & Patrick Moore present the Marjory Stephenson Prize Lecture ‘Old themes and new variations in human tumour virology’ on 27 March at the Society for General Microbiology’s Spring Conference 2012 in Dublin.
Actinic keratosis is no laughing matter – untreated, up to 20% of cases may pregress to skin cancer. At the same time, if this paper had been published on 1st April (it wasn’t) I would have had my doubts. I’ve seen some interesting virus sampling protocols in my time (bear in mind we sequenced the horse faeces virome), but this one is pretty unique. As a side benefit, also reduces the risk of monobrow.
