http://www.virologyj.com The most accessed research articles published by Virology Journal 2012-05-08T00:00:00Z Background: The carboxyl terminal of Epstein-Barr virus (EBV) ZEBRA protein (also termed BZLF-1 encoded replication protein Zta or ZEBRA) binds to both NF-κB and p53. The authors have previously suggested that this interaction results from an ankyrin-like region of the ZEBRA protein since ankyrin proteins such as IκB interact with NF-κB and p53 proteins. These interactions may play a role in immunopathology and viral carcinogenesis in B lymphocytes as well as other cell types transiently infected by EBV such as T lymphocytes, macrophages and epithelial cells. Methods: Randomization of the ZEBRA terminal amino acid sequence followed by statistical analysis suggest that the ZEBRA carboxyl terminus is most closely related to ankyrins of the invertebrate cactus IκB-like protein. This observation is consistent with an ancient origin of ZEBRA resulting from a recombination event between an ankyrin regulatory protein and a fos/jun DNA binding factor. In silico modeling of the partially solved ZEBRA carboxyl terminus structure using PyMOL software demonstrate that the carboxyl terminus region of ZEBRA can form a polymorphic structure termed ZANK (ZEBRA ANKyrin-like region) similar to two adjacent IκB ankyrin domains. Conclusions: Viral capture of an ankyrin-like domain provides a mechanism for ZEBRA binding to proteins in the NF-κB and p53 transcription factor families, and also provides support for a process termed "Ping-Pong Evolution" in which DNA viruses such as EBV are formed by exchange of information with the host genome. An amino acid polymorphism in the ZANK region is identified in ZEBRA from tumor cell lines including Akata that could alter binding of Akata ZEBRA to the p53 tumor suppressor and other ankyrin binding protein, and a novel model of antagonistic binding interactions between ZANK and the DNA binding regions of ZEBRA is suggested that may be explored in further biochemical and molecular biological models of viral replication. http://www.virologyj.com/content/8/1/422 David Dreyfus Yang Liu Lucy Ghoda Joseph Chang Virology Journal 2011, null:422 2011-09-05T00:00:00Z doi:10.1186/1743-422X-8-422 /content/figures/1743-422X-8-422-toc.gif Virology Journal 1743-422X ${item.volume} 422 2011-09-05T00:00:00Z XML Herpes simplex virus (HSV) infection is one of the most common viral sexually transmitted diseases worldwide. The first time infection of the mother may lead to severe illness in pregnancy and may be associated with virus transmission from mother to foetus/newborn.Since the incidence of this sexually transmitted infection continues to rise and because the greatest incidence of herpes simplex virus infections occur in women of reproductive age, the risk of maternal transmission of the virus to the foetus or neonate has become a major health concern.On these purposes the Authors of this review looked for the medical literature and pertinent publications to define the status of art regarding the epidemiology, the diagnosis, the therapy and the prevention of HSV in pregnant women and neonate. Special emphasis is placed upon the importance of genital herpes simplex virus infection in pregnancy and on the its prevention to avoid neonatal HSV infections. http://www.virologyj.com/content/6/1/40 Elena Anzivino Daniela Fioriti Monica Mischitelli Anna Bellizzi Valentina Barucca Fernanda Chiarini Valeria Pietropaolo Virology Journal 2009, null:40 2009-04-06T00:00:00Z doi:10.1186/1743-422X-6-40 /content/figures/1743-422X-6-40-toc.gif Virology Journal 1743-422X ${item.volume} 40 2009-04-06T00:00:00Z XML Background: The visualization of viral proteins has been hindered by the resolution limit of conventional fluorescent microscopes, as the dimension of any single fluorescent signal is often greater than most virion particles. Super-resolution microscopy has the potential to unveil the distribution of proteins at the resolution approaching electron microscopy without relying on morphological features of existing features of the biological specimen. Results: Using direct stochastic optical reconstruction microscopy (dSTORM) to achieve a lateral resolution of 15-20 nm, we quantified the 2-D molecular distribution of the major structural proteins of the infectious human immunodeficiency virus type 1 (HIV-1) before and after infection of lymphoid cells. We determined that the HIV-1 matrix and capsid proteins undergo restructuring soon after HIV-1 infection. Conclusions: This study provides the proof-of-concept for the use of dSTORM to visualize the changes in the molecular distribution of viral proteins during an infection. http://www.virologyj.com/content/9/1/84 Cândida Pereira Jérémie Rossy Dylan Owen Johnson Mak Katharina Gaus Virology Journal 2012, null:84 2012-05-02T00:00:00Z doi:10.1186/1743-422X-9-84 /content/figures/1743-422X-9-84-toc.gif Virology Journal 1743-422X ${item.volume} 84 2012-05-02T00:00:00Z PDF Inactive carriers forms the largest group in chronic HBV infected patients. Around 300 million people are inactive carriers The inactive HBsAg carrier state is diagnosed by absence of HBeAg and presence of anti-HBe, undetectable or low levels of HBV DNA in PCR-based assays, repeatedly normal ALT levels, and minimal or no necroinflammation, slight fibrosis, or even normal histology on biopsy. Inactive cirrhosis may be present in patients who had active liver disease during the replicative phase of infection. The prognosis of the inactive HBsAg carrier state is usually benign. Long-term follow- up (up to 18 years) of these carriers has indicated that the vast majority show sustained biochemical remission and very low risk of cirrhosis or hepatocellular carcinoma (HCC). Rarely, patients, even noncirrhotics, may develop liver cancer during the inactive HBsAg carrier state. In addition, approximately 20 to 30% of persons in the inactive HBsAg carrier state may undergo spontaneous reactivation of hepatitis B during follow-up. Multiple episodes of reactivation or sustained reactivation can cause progressive hepatic damage and even hepatic decompensation. Introduction http://www.virologyj.com/content/2/1/82 Sanjeev Sharma Nitin Saini Yogesh Chwla Virology Journal 2005, null:82 2005-09-28T00:00:00Z doi:10.1186/1743-422X-2-82 /content/figures/1743-422X-2-82-toc.gif Virology Journal 1743-422X ${item.volume} 82 2005-09-28T00:00:00Z XML Background: Hepatitis B virus (HBV) is still one of the serious infectious risks for the blood transfusion safety in China. One plausible reason is the emergence of the variants in the major antigenic alpha determinant within the major hydrophilic region (MHR) of hepatitis B surface antigen (HBsAg), which have been assumed to evade the immune surveillance and pose a challenge to the disease diagnosis. It is well documented that some commercial ELISA kits could detect the wild-type but not the mutant viruses. The high prevalence of HBV in China also impaired the application of nucleic acid testing (NAT) in the improvement of blood security. Molecular epidemiological study of HBsAg variations in China is still limited. This study was designed to identify the prevalence of mutations in the HBsAg in voluntary blood donors in Nanjing, China. Methods: A total of 20,326 blood units were enrolled in this study, 39 donors were positive for HBV S gene in the nested-PCR. Mutations in the major hydrophilic region (MHR; aa 99-169) were identified by direct sequencing of S region. Results: Among of 20,326 blood units in the Red Cross Transfusion Center of Nanjing from October 2008 to April 2009, 296 samples (1.46%, 296/20,326) were HBsAg positive in the 2 successive rounds of the ELISA test. In these HBsAg positive units, HBV S gene could be successfully amplified from 39 donors (13.18%, 39/296) in the nested-PCR. Sequence analysis revealed that 32 strains (82.1%, 32/39) belong to genotype B, 7 strains (17.9%, 7/39) to genotype C. Besides well known G145R, widely dispersed variations in the MHR of S region, were observed in 20 samples of all the strains sequenced. Conclusions: HBV/B and HBV/C are dominant in Nanjing, China. The mutations in the MHR of HBsAg associated with disease diagnosis are common. http://www.virologyj.com/content/9/1/82 Yong-lin Yang Qiang Fu Ming-shun Zhang Jie Cai Gui-ming Ma Zu-hu Huang Xu-bing Cai Virology Journal 2012, null:82 2012-04-14T00:00:00Z doi:10.1186/1743-422X-9-82 /content/figures/1743-422X-9-82-toc.gif Virology Journal 1743-422X ${item.volume} 82 2012-04-14T00:00:00Z XML Background: Diagnosis of West Nile virus (WNV) infections is often difficult due to the extensive antigenic cross-reactivity among flaviviruses, especially in geographic regions where two or more of these viruses are present causing sequential infections. The purpose of this study was to characterize a panel of monoclonal antibodies (MAbs) produced against WNV to verify their applicability in WNV diagnosis and in mapping epitope targets of neutralizing MAbs. Methods: Six MAbs were produced and characterized by isotyping, virus-neutralization, western blotting and MAb-epitope competition. The MAb reactivity against various WNVs belonging to lineage 1 and 2 and other related flaviviruses was also evaluated. The molecular basis of epitopes recognized by neutralizing MAbs was defined through the selection and sequencing of MAb escape mutants. Competitive binding assays between MAbs and experimental equine and chicken sera were designed to identify specific MAb reaction to epitopes with high immunogenicity. Results: All MAbs showed stronger reactivity with all WNVs tested and good competition for antigen binding in ELISA tests with WNV-positive equine and chicken sera. Four MAbs (3B2, 3D6, 4D3, 1C3) resulted specific for WNV, while two MAbs (2A8, 4G9) showed cross-reaction with Usutu virus. Three MAbs (3B2, 3D6, 4D3) showed neutralizing activity. Sequence analysis of 3B2 and 3D6 escape mutants showed an amino acid change at E307 (Lys -> Glu) in the E protein gene, whereas 4D3 variants identified mutations encoding amino acid changed at E276 (Ser -> Ile) or E278 (Thr -> Ile). 3B2 and 3D6 mapped to a region on the lateral surface of domain III of E protein, which is known to be a specific and strong neutralizing epitope for WNV, while MAb 4D3 recognized a novel specific neutralizing epitope on domain II of E protein that has not previously been described with WNV MAbs. Conclusions: MAbs generated in this study can be applied to various analytical methods for virological and serological WNV diagnosis. A novel WNV-specific and neutralizing MAb (4D3) directed against the unknown epitope on domain II of E protein can be useful to better understand the role of E protein epitopes involved in the mechanism of WNV neutralization. http://www.virologyj.com/content/9/1/81 Davide Lelli Ana Moreno Emiliana Brocchi Enrica Sozzi Lorenzo Capucci Elena Canelli Ilaria Barbieri Herve Zeller Paolo Cordioli Virology Journal 2012, null:81 2012-04-13T00:00:00Z doi:10.1186/1743-422X-9-81 /content/figures/1743-422X-9-81-toc.gif Virology Journal 1743-422X ${item.volume} 81 2012-04-13T00:00:00Z PDF 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, null:29 2008-02-25T00:00:00Z doi:10.1186/1743-422X-5-29 /content/figures/1743-422X-5-29-toc.gif Virology Journal 1743-422X ${item.volume} 29 2008-02-25T00:00:00Z XML Recently it has been recognized that bacteriophages, the natural predators of bacteria can be used efficiently in modern biotechnology. They have been proposed as alternatives to antibiotics for many antibiotic resistant bacterial strains. Phages can be used as biocontrol agents in agriculture and petroleum industry. Moreover phages are used as vehicles for vaccines both DNA and protein, for the detection of pathogenic bacterial strain, as display system for many proteins and antibodies. Bacteriophages are diverse group of viruses which are easily manipulated and therefore they have potential uses in biotechnology, research, and therapeutics. The aim of this review article is to enable the wide range of researchers, scientists, and biotechnologist who are putting phages into practice, to accelerate the progress and development in the field of biotechnology. http://www.virologyj.com/content/9/1/9 Irshad Haq Waqas Nasir Chaudhry Maha Nadeem Akhtar Saadia Andleeb Ishtiaq Qadri Virology Journal 2012, null:9 2012-01-10T00:00:00Z doi:10.1186/1743-422X-9-9 /content/figures/1743-422X-9-9-toc.gif Virology Journal 1743-422X ${item.volume} 9 2012-01-10T00:00:00Z XML Background: Nuclear factor-kappaB (NF-kappaB) is an inducible transcription factor that plays a key role in inflammation and immune responses, as well as in the regulation of cell proliferation and survival. Previous studies by our group and others have demonstrated that Porcine reproductive and respiratory syndrome virus (PRRSV) infection could activate NF-kappaB in MARC-145 cells and alveolar macrophages. The nucleocapsid (N) protein was identified as an NF-kappaB activator among the structural proteins encoded by PRRSV; however, it remains unclear whether the nonstructural proteins (Nsps) contribute to NF-kappaB activation. In this study, we identified which Nsps can activate NF-kappaB and investigated the potential mechanism(s) by which they act. Results: By screening the individual Nsps of PRRSV strain WUH3, Nsp2 exhibited great potential to activate NF-kappaB in MARC-145 and HeLa cells. Overexpression of Nsp2 induced IkappaBalpha degradation and nuclear translocation of NF-kappaB. Furthermore, Nsp2 also induced NF-kappaB-dependent inflammatory factors, including interleukin (IL)-6, IL-8, COX-2, and RANTES. Compared with the Nsp2 of the classical PRRSV strain, the Nsp2 of highly pathogenic PRRSV (HP-PRRSV) strains that possess a 30 amino acid (aa) deletion in Nsp2 displayed greater NF-kappaB activation. However, the 30-aa deletion was demonstrated to not be associated with NF-kappaB activation. Further functional domain analyses revealed that the hypervariable region (HV) of Nsp2 was essential for NF-kappaB activation. Conclusions: Taken together, these data indicate that PRRSV Nsp2 is a multifunctional protein participating in the modulation of host inflammatory response, which suggests an important role of Nsp2 in pathogenesis and disease outcomes. http://www.virologyj.com/content/9/1/83 Ying Fang Liurong Fang Yang Wang Yingying Lei Rui Luo Dang Wang Huanchun Chen Shaobo Xiao Virology Journal 2012, null:83 2012-04-30T00:00:00Z doi:10.1186/1743-422X-9-83 /content/figures/1743-422X-9-83-toc.gif Virology Journal 1743-422X ${item.volume} 83 2012-04-30T00:00:00Z PDF Background: Influenza virus undergoes rapid evolution by both antigenic shift and antigenic drift. Antibodies, particularly those binding near the receptor-binding site of hemagglutinin (HA) or the neuraminidase (NA) active site, are thought to be the primary defense against influenza infection, and mutations in antibody binding sites can reduce or eliminate antibody binding. The binding of antibodies to their cognate antigens is governed by such biophysical properties of the interacting surfaces as shape, non-polar and polar surface area, and charge. Methods: To understand forces shaping evolution of influenza virus, we have examined HA sequences of human influenza A and B viruses, assigning each amino acid values reflecting total accessible surface area, non-polar and polar surface area, and net charge due to the side chain. Changes in each of these values between neighboring sequences were calculated for each residue and mapped onto the crystal structures. Results: Areas of HA showing the highest frequency of changes agreed well with previously identified antigenic sites in H3 and H1 HAs, and allowed us to propose more detailed antigenic maps and novel antigenic sites for H1 and influenza B HA. Changes in biophysical properties differed between HAs of different subtypes, and between different antigenic sites of the same HA. For H1, statistically significant differences in several biophysical quantities compared to residues lying outside antigenic sites were seen for some antigenic sites but not others. Influenza B antigenic sites all show statistically significant differences in biophysical quantities for all antigenic sites, whereas no statistically significant differences in biophysical quantities were seen for any antigenic site is seen for H3. In many cases, residues previously shown to be under positive selection at the genetic level also undergo rapid change in biophysical properties. Conclusions: The biophysical consequences of amino acid changes introduced by antigenic drift vary from subtype to subtype, and between different antigenic sites. This suggests that the significance of antibody binding in selecting new variants may also be variable for different antigenic sites and influenza subtypes. http://www.virologyj.com/content/9/1/91 Stephen Stray Lindsey Pittman Virology Journal 2012, null:91 2012-05-08T00:00:00Z doi:10.1186/1743-422X-9-91 /content/figures/1743-422X-9-91-toc.gif Virology Journal 1743-422X ${item.volume} 91 2012-05-08T00:00:00Z PDF