http://www.virologyj.com The most accessed research articles published by Virology Journal 2010-03-04T00:00:00Z This is an RSS newsfeed from BioMed Central It is intended to be used with an RSS reader. For more information about RSS newsfeeds from BioMed Central, visit http://www.biomedcentral.com/info/about/rss/ The swine-origin influenza A (H1N1) virus that appeared in 2009 and was first found in human beings in Mexico, is a reassortant with at least three parents. Six of the genes are closest in sequence to those of H1N2 'triple-reassortant' influenza viruses isolated from pigs in North America around 1999-2000. Its other two genes are from different Eurasian 'avian-like' viruses of pigs; the NA gene is closest to H1N1 viruses isolated in Europe in 1991-1993, and the MP gene is closest to H3N2 viruses isolated in Asia in 1999-2000. The sequences of these genes do not directly reveal the immediate source of the virus as the closest were from isolates collected more than a decade before the human pandemic started. The three parents of the virus may have been assembled in one place by natural means, such as by migrating birds, however the consistent link with pig viruses suggests that human activity was involved. We discuss a published suggestion that unsampled pig herds, the intercontinental live pig trade, together with porous quarantine barriers, generated the reassortant. We contrast that suggestion with the possibility that laboratory errors involving the sharing of virus isolates and cultured cells, or perhaps vaccine production, may have been involved. Gene sequences from isolates that bridge the time and phylogenetic gap between the new virus and its parents will distinguish between these possibilities, and we suggest where they should be sought. It is important that the source of the new virus be found if we wish to avoid future pandemics rather than just trying to minimize the consequences after they have emerged. Influenza virus is a very significant zoonotic pathogen. Public confidence in influenza research, and the agribusinesses that are based on influenza's many hosts, has been eroded by several recent events involving the virus. Measures that might restore confidence include establishing a unified international administrative framework coordinating surveillance, research and commercial work with this virus, and maintaining a registry of all influenza isolates. http://www.virologyj.com/content/6/1/207 Adrian Gibbs John Armstrong Jean Downie Virology Journal 2009, 6:207 2009-11-24T00:00:00Z doi:10.1186/1743-422X-6-207 Virology Journal 1743-422X 6 207 2009-11-24T00:00:00Z XML The epidemiology of influenza swarms with incongruities, incongruities exhaustively detailed by the late British epidemiologist, Edgar Hope-Simpson. He was the first to propose a parsimonious theory explaining why influenza is, as Gregg said, "seemingly unmindful of traditional infectious disease behavioral patterns." Recent discoveries indicate vitamin D upregulates the endogenous antibiotics of innate immunity and suggest that the incongruities explored by Hope-Simpson may be secondary to the epidemiology of vitamin D deficiency. We identify – and attempt to explain – nine influenza conundrums: (1) Why is influenza both seasonal and ubiquitous and where is the virus between epidemics? (2) Why are the epidemics so explosive? (3) Why do they end so abruptly? (4) What explains the frequent coincidental timing of epidemics in countries of similar latitude? (5) Why is the serial interval obscure? (6) Why is the secondary attack rate so low? (7) Why did epidemics in previous ages spread so rapidly, despite the lack of modern transport? (8) Why does experimental inoculation of seronegative humans fail to cause illness in all the volunteers? (9) Why has influenza mortality of the aged not declined as their vaccination rates increased? We review recent discoveries about vitamin D's effects on innate immunity, human studies attempting sick-to-well transmission, naturalistic reports of human transmission, studies of serial interval, secondary attack rates, and relevant animal studies. We hypothesize that two factors explain the nine conundrums: vitamin D's seasonal and population effects on innate immunity, and the presence of a subpopulation of "good infectors." If true, our revision of Edgar Hope-Simpson's theory has profound implications for the prevention of influenza. http://www.virologyj.com/content/5/1/29 John Cannell Michael Zasloff Cedric Garland Robert Scragg Edward Giovannucci Virology Journal 2008, 5:29 2008-02-25T00:00:00Z doi:10.1186/1743-422X-5-29 Virology Journal 1743-422X 5 29 2008-02-25T00:00:00Z XML Background: Hepatitis C virus (HCV) is a blood-borne flavivirus that infects many millions of people worldwide. Relatively little is known, however, concerning the stability of HCV and reliable procedures for inactivating this virus. Methods: In the current study, the thermostability of cell culture-derived HCV (HCVcc, JFH-1 strain) under different environmental temperatures (37°C, room temperature, and 4°C) and the ability of heat, UVC light irradiation, and aldehyde and detergent treatments to inactivate HCVcc were evaluated. The infectious titers of treated viral samples were determined by focus-forming unit (FFU) assay using an indirect immunofluorescence assay for HCV NS3 in hepatoma Huh7-25-CD81 cells highly permissive for HCVcc infection. MTT cytotoxicity assay was performed to determine the concentrations of aldehydes or detergents at which they were no longer cytotoxic. Results: HCVcc in culture medium was found to survive 37°C and room temperature (RT, 25 ± 2°C) for 2 and 16 days, respectively, while the virus was relatively stable at 4°C without drastic loss of infectivity for at least 6 weeks. HCVcc in culture medium was sensitive to heat and could be inactivated in 8 and 4 min when incubated at 60°C and 65°C, respectively. However, at 56°C, 40 min were required to eliminate HCVcc infectivity. Addition of normal human serum to HCVcc did not significantly alter viral stability at RT or its susceptibility to heat. UVC light irradiation (wavelength = 253.7 nm) with an intensity of 450 μW/cm2 efficiently inactivated HCVcc within 2 min. Exposures to formaldehyde, glutaraldehyde, ionic or nonionic detergents all destroyed HCVcc infectivity effectively, regardless of whether the treatments were conducted in the presence of cell culture medium or human serum. Conclusions: The results provide quantitative evidence for the potential use of a variety of approaches for inactivating HCV. The ability of HCVcc to survive ambient temperatures warrants precautions in handling and disposing of objects and materials that may have been contaminated with HCV. http://www.virologyj.com/content/7/1/40 Hongshuo Song Jin Li Shuang Shi Ling Yan Hui Zhuang Kui Li Virology Journal 2010, 7:40 2010-02-18T00:00:00Z doi:10.1186/1743-422X-7-40 Virology Journal 1743-422X 7 40 2010-02-18T00:00:00Z XML Background: Throughout the history of human influenza pandemics, pigs have been considered the most likely "mixing vessel" for reassortment between human and avian influenza viruses (AIVs). However, the replication efficiencies of influenza viruses from various hosts, as well as the expression of sialic acid (Sia) receptor variants in the entire porcine respiratory tract have never been studied in detail. Therefore, we established porcine nasal, tracheal, bronchial and lung explants, which cover the entire porcine respiratory tract with maximal similarity to the in vivo situation. Subsequently, we assessed virus yields of three porcine, two human and six AIVs in these explants. Since our results on virus replication were in disagreement with the previously reported presence of putative avian virus receptors in the trachea, we additionally studied the distribution of sialic acid receptors by means of lectin histochemistry. Human (Siaα2-6Gal) and avian virus receptors (Siaα2-3Gal) were identified with Sambucus Nigra and Maackia amurensis lectins respectively. Results: Compared to swine and human influenza viruses, replication of the AIVs was limited in all cultures but most strikingly in nasal and tracheal explants. Results of virus titrations were confirmed by quantification of infected cells using immunohistochemistry. By lectin histochemistry we found moderate to abundant expression of the human-like virus receptors in all explant systems but minimal binding of the lectins that identify avian-like receptors, especially in the nasal, tracheal and bronchial epithelium. Conclusions: The species barrier that restricts the transmission of influenza viruses from one host to another remains preserved in our porcine respiratory explants. Therefore this system offers a valuable alternative to study virus and/or host properties required for adaptation or reassortment of influenza viruses. Our results indicate that, based on the expression of Sia receptors alone, the pig is unlikely to be a more appropriate mixing vessel for influenza viruses than humans. We conclude that too little is known on the exact mechanism and on predisposing factors for reassortment to assess the true role of the pig in the emergence of novel influenza viruses. http://www.virologyj.com/content/7/1/38 Sjouke Van Poucke John Nicholls Hans Nauwynck Kristien Van Reeth Virology Journal 2010, 7:38 2010-02-16T00:00:00Z doi:10.1186/1743-422X-7-38 Virology Journal 1743-422X 7 38 2010-02-16T00:00:00Z XML The current pandemic influenza A H1N1 2009 (pH1N1) was first recognized in humans with acute respiratory diseases in April 2009 in Mexico, in swine in Canada in June, 2009 with respiratory disease, and in turkeys in Chile in June 2009 with a severe drop in egg production. Several experimental studies attempted to reproduce the disease in turkeys, but failed to produce respiratory infection in turkeys using standard inoculation routes. We demonstrated that pH1N1 virus can infect the reproductive tract of turkey hens after experimental intrauterine inoculation, causing decreased egg production. This route of exposure is realistic in modern turkey production because turkey hens are handled once a week for intrauterine insemination in order to produce fertile eggs. This understanding of virus exposure provides an improved understanding of the pathogenesis of the disease and can improve poultry husbandry to prevent disease outbreaks. http://www.virologyj.com/content/7/1/27 Mary Pantin-Jackwood Jamie Wasilenko Erica Spackman David Suarez David Swayne Virology Journal 2010, 7:27 2010-02-03T00:00:00Z doi:10.1186/1743-422X-7-27 Virology Journal 1743-422X 7 27 2010-02-03T00:00:00Z XML Background: It is widely considered that the multifunctional NS1 protein of influenza A viruses contributes significantly disease pathogenesis by modulating a number of virus and host-cell processes, but it is highly controversial whether this non-structural protein is a proapoptotic or antiapoptotic factor in infected cells. Results: NS1 protein of influenza A/chicken/Jilin/2003 virus, a highly pathogenic H5N1 strain, could induce apoptosis in the carcinomic human alveolar basal epithelial cells (A549) by electron microscopic and flow cytometric analyses. NS1 protein-triggered apoptosis in A549 cells is via caspase-dependent pathway. Conclusions: Influenza A virus NS1 protein serves as a strong inducer of apoptosis in infected human respiratory epithelial cells and plays a critical role in disease pathogenesis. http://www.virologyj.com/content/7/1/51 Chuanfu Zhang Yutao Yang Xiaowei Zhou Xuelin Liu Hongbin Song Yuxian He Peitang Huang Virology Journal 2010, 7:51 2010-03-03T00:00:00Z doi:10.1186/1743-422X-7-51 Virology Journal 1743-422X 7 51 2010-03-03T00:00:00Z PDF Background: The Hepatitis B Virus X protein (HBx) plays a major role in hepatocellular carcinoma (HCC) development, however, its contribution to tumor invasion and metastasis has not been established so far. Heat shock protein 90alpha (HSP90alpha) isoform is an ATP-dependent molecular chaperone that maintains the active conformation of client oncoproteins in cancer cells, which is abundantly expressed in HCC, especially in hepatitis B virus (HBV)-related tumors, might be involved in tumor progression. Methods: The levels of HSP90alpha, extracellular signal-regulated kinase 1/2 (ERK1/2), phosphorylated ERK1/2 (p-ERK1/2) and c-Myc in HBx-transfected HepG2 cells were determined by western blots analysis. The endogenous ERKs activity was demonstrated by ELISA assay. The regulation of c-Myc-mediated HSP90alpha promoter transactivation by HBx was evaluated through electrophoretic mobility shift analysis (EMSA). The c-Myc-mediated HSP90alpha transcription was analysed by promoter assay. The HBx-expressing cells were transfected with specific small interference RNA (siRNA) against c-Myc. The in vitro invasion potentials of cells were evaluated by Transwell cell invasion assay. Results: HBx induces HSP90alpha expression at the transcription level. The induction effect of HBx was inhibited after treatment with c-Myc inhibitor, 10058-F4. In addition, the luciferase activity of the HSP90alpha promoter analysis revealed that the HBx is directly involved in the c-Myc-mediated transcriptional activation of HSP90alpha. Furthermore, HBx induces c-Myc expression by activation of Ras/Raf/ERK1/2 cascades, which in turn results in activation of the c-Myc-mediated HSP90alpha promoter and subsequently up-regulation of the HSP90alpha expression. Overexpression of HSP90alpha in HBx-transfected cells enhances tumor cells invasion. siRNA-mediated c-Myc knockdown in HBx-transfected cells significantly suppressed HSP90alpha expression and cells invasion in vitro. Conclusion: These results demonstrate the ability of HBx to promote tumor cells invasion by a mechanism involving the up-regulation of HSP90alpha and provide new insights into the mechanism of action of HBx and its involvement in tumor metastasis and recurrence of HCC. http://www.virologyj.com/content/7/1/45 Weihua Li Xiaohui Miao Zhongtian Qi Wenting Zeng Jianxin Liang Zengwei Liang Virology Journal 2010, 7:45 2010-02-20T00:00:00Z doi:10.1186/1743-422X-7-45 Virology Journal 1743-422X 7 45 2010-02-20T00:00:00Z PDF Measles, caused by measles virus (MeV), is a common infection in children. MeV is a member of the genus Morbillivirus and is most closely related to rinderpest virus (RPV), which is a pathogen of cattle. MeV is thought to have evolved in an environment where cattle and humans lived in close proximity. Understanding the evolutionary history of MeV could answer questions related to divergence times of MeV and RPV.We investigated divergence times using relaxed clock Bayesian phylogenetics. Our estimates reveal that MeV had an evolutionary rate of 6.0 - 6.5 x 104 substitutions/site/year. It was concluded that the divergence time of the most recent common ancestor of current MeV was the early 20th century. And, divergence between MeV and RPV occurred around the 11th to 12th centuries. The result was unexpected because emergence of MeV was previously considered to have occurred in the prehistoric age.MeV may have originated from non-human species and caused emerging infectious diseases around the 11th to 12th centuries. In such cases, investigating measles would give important information about the course of emerging infectious diseases. http://www.virologyj.com/content/7/1/52 Yuki Furuse Akira Suzuki Hitoshi Oshitani Virology Journal 2010, 7:52 2010-03-04T00:00:00Z doi:10.1186/1743-422X-7-52 Virology Journal 1743-422X 7 52 2010-03-04T00:00:00Z PDF Background: EV71 occasionally cause a series of severe neurological symptoms, including aseptic meningitis, encephalitis, and poliomyelitis-like paralysis. However, the neurological destruction mechanism was remained to be clarified. This study described the cross reaction between EV71 induced IgG and human brain tissue. Results: Cross reaction of the IgG from 30 EV71 infected patients' sera to human tissues of cerebra was observed, which suggested that some EV71 antigens could induce IgG cross-reactivity to human cerebra. To identify the regions of EV71 virus that containing above antigens, the polypeptide of virus was divided into 19 peptides by expression in prokaryotes cell. Mouse anti-sera of these peptides was prepared and applied in immunohistochemical staining with human adult and fetus brain tissue, respectively. The result indicated the 19 peptides can be classified into three groups: strong cross-reactivity, weak cross-reactivity and no cross-reactivity with human brain tissue according the cross reaction activity. Then, the increased Blood Brain Barrier (BBB) permeability and permits IgG entry in neonatal mice after EV71 infection was determined. Conclusion: EV71 induced IgG could enter BBB and cross-reacted with brain tissue in EV71 infected neonatal mice, and then the peptides of EV71 that could induce cross-reactivity with brain tissue were identified, which should be avoided in future vaccine designing. http://www.virologyj.com/content/7/1/47 Chun Shi Jia Jiang Ning Liu Wan Bo Li Chun Mei Ma Shu Zhu Lin Yi Hao Xue Zhong Gao Xiao Lin Liu Yan Feng Xu Lian Feng Zhang Chuan Qin Virology Journal 2010, 7:47 2010-02-22T00:00:00Z doi:10.1186/1743-422X-7-47 Virology Journal 1743-422X 7 47 2010-02-22T00:00:00Z PDF Rubella virus (RV) causes severe congenital defects when acquired during the first trimester of pregnancy. RV cytopathic effect has been shown to be due to caspase-dependent apoptosis in a number of susceptible cell lines, and it has been suggested that this apoptotic induction could be a causal factor in the development of such defects. Often the outcome of apoptotic stimuli is dependent on apoptotic, proliferative and survival signaling mechanisms in the cell. Therefore we investigated the role of phosphoinositide 3-kinase (PI3K)-Akt survival signaling and Ras-Raf-MEK-ERK proliferative signaling during RV-induced apoptosis in RK13 cells. Increasing levels of phosphorylated ERK, Akt and GSK3β were detected from 24–96 hours post-infection, concomitant with RV-induced apoptotic signals. Inhibition of PI3K-Akt signaling reduced cell viability, and increased the speed and magnitude of RV-induced apoptosis, suggesting that this pathway contributes to cell survival during RV infection. In contrast, inhibition of the Ras-Raf-MEK-ERK pathway impaired RV replication and growth and reduced RV-induced apoptosis, suggesting that the normal cellular growth is required for efficient virus production. http://www.virologyj.com/content/2/1/1 Samantha Cooray Li Jin Jennifer Best Virology Journal 2005, 2:1 2005-01-04T00:00:00Z doi:10.1186/1743-422X-2-1 Virology Journal 1743-422X 2 1 2005-01-04T00:00:00Z XML