Advances in Virology http://www.hindawi.com The latest articles from Hindawi Publishing Corporation © 2014 , Hindawi Publishing Corporation . All rights reserved. Screening of Viral Pathogens from Pediatric Ileal Tissue Samples after Vaccination Sun, 23 Mar 2014 12:57:25 +0000 http://www.hindawi.com/journals/av/2014/720585/ In 2010, researchers reported that the two US-licensed rotavirus vaccines contained DNA or DNA fragments from porcine circovirus (PCV). Although PCV, a common virus among pigs, is not thought to cause illness in humans, these findings raised several safety concerns. In this study, we sought to determine whether viruses, including PCV, could be detected in ileal tissue samples of children vaccinated with one of the two rotavirus vaccines. A broad spectrum, novel DNA detection technology, the Lawrence Livermore Microbial Detection Array (LLMDA), was utilized, and confirmation of viral pathogens using the polymerase chain reaction (PCR) was conducted. The LLMDA technology was recently used to identify PCV from one rotavirus vaccine. Ileal tissue samples were analyzed from 21 subjects, aged 15–62 months. PCV was not detected in any ileal tissue samples by the LLMDA or PCR. LLMDA identified a human rotavirus A from one of the vaccinated subjects, which is likely due to a recent infection from a wild type rotavirus. LLMDA also identified human parechovirus, a common gastroenteritis viral infection, from two subjects. Additionally, LLMDA detected common gastrointestinal bacterial organisms from the Enterobacteriaceae, Bacteroidaceae, and Streptococcaceae families from several subjects. This study provides a survey of viral and bacterial pathogens from pediatric ileal samples, and may shed light on future studies to identify pathogen associations with pediatric vaccinations. Laura Hewitson, James B. Thissen, Shea N. Gardner, Kevin S. McLoughlin, Margaret K. Glausser, and Crystal J. Jaing Copyright © 2014 Laura Hewitson et al. All rights reserved. Characterization of the Protective HIV-1 CTL Epitopes and the Corresponding HLA Class I Alleles: A Step towards Designing CTL Based HIV-1 Vaccine Tue, 18 Mar 2014 07:57:56 +0000 http://www.hindawi.com/journals/av/2014/321974/ Human immunodeficiency virus (HIV) possesses a major threat to the human life largely due to the unavailability of an efficacious vaccine and poor access to the antiretroviral drugs against this deadly virus. High mutation rate in the viral genome underlying the antigenic variability of the viral proteome is the major hindrance as far as the antibody based vaccine development is concerned. Although the exact mechanism by which CTL epitopes and the restricting HLA alleles mediate their action towards slow disease progression is still not clear, the important CTL restricted epitopes for controlling viral infections can be utilized in future vaccine design. This study was designed for the characterization the HIV-1 optimal CTL epitopes and their corresponding HLA alleles. CTL epitope cluster distribution analysis revealed only two HIV-1 proteins, namely, Nef and Gag, which have significant cluster forming capacity. We have found the role of specific HLA supertypes such as HLA B*07, HLA B*58, and HLA A*03 in selecting the hydrophobic and conserved amino acid positions within Nef and Gag proteins, to be presented as epitopes. The analyses revealed that the clusters of optimal epitopes for Nef and p24 proteins of HIV-1 could potentially serve as a source of vaccine. Sajib Chakraborty, Taibur Rahman, and Rajib Chakravorty Copyright © 2014 Sajib Chakraborty et al. All rights reserved. Comment on “Emergence of Hepatitis B Virus Genotype F in Aligarh Region of North India” Mon, 17 Mar 2014 09:12:25 +0000 http://www.hindawi.com/journals/av/2014/637439/ Sibnarayan Datta Copyright © 2014 Sibnarayan Datta. All rights reserved. Genotyping of HCV RNA Reveals That 3a Is the Most Prevalent Genotype in Mardan, Pakistan Wed, 26 Feb 2014 06:52:05 +0000 http://www.hindawi.com/journals/av/2014/606201/ The clinical outcomes of patients infected with hepatitis C virus (HCV) range from acute resolving hepatitis to chronic liver diseases such as liver cirrhosis or hepatocellular carcinoma. Identification of the infecting virus genotype is indispensable for the exploration of many aspects of HCV infection, including epidemiology, pathogenesis, and response to antiviral therapy. 1419 individuals were screened for anti-HCV in this study, of which 166 (11.7%) were found reactive by ICT (Immunochromatographic test). These 166 anti-HCV positive and 26 normal individuals were further analyzed. RNA was extracted from serum and reverse-transcribed to cDNA and the core region of HCV genome was targeted and amplified by multiplex PCR. HCV RNA was detected in 121 individuals, of which 87 were male and 34 were female. Genotype 3a was the most prevalent among all the genotypes observed followed by 3b. Genotypes 1a, 2a, and 2b were found in 10.89%, 13.22%, and 6.61% patients, respectively. 25.41% of the HCV RNA positive samples were not typed. 6.05% of patients were found having mixed genotypes. These findings will not only help the physicians to prescribe more appropriate treatment for the HCV infection but will also draw the attention of health-related policy makers to devise strategies to curb the disease more effectively. Sajid Ali, Ayaz Ahmad, Raham Sher Khan, Sanaullah Khan, Muhammad Hamayun, Sumera Afzal Khan, Amjad Iqbal, Abid Ali Khan, Abdul Wadood, Taj Ur Rahman, and Ali Hydar Baig Copyright © 2014 Sajid Ali et al. All rights reserved. Mutations in the H, F, or M Proteins Can Facilitate Resistance of Measles Virus to Neutralizing Human Anti-MV Sera Tue, 04 Feb 2014 15:31:51 +0000 http://www.hindawi.com/journals/av/2014/205617/ Although there is currently no evidence of emerging strains of measles virus (MV) that can resist neutralization by the anti-MV antibodies present in vaccinees, certain mutations in circulating wt MV strains appear to reduce the efficacy of these antibodies. Moreover, it has been hypothesized that resistance to neutralization by such antibodies could allow MV to persist. In this study, we use a novel in vitro system to determine the molecular basis of MV’s resistance to neutralization. We find that both wild-type and laboratory strain MV variants that escape neutralization by anti-MV polyclonal sera possess multiple mutations in their H, F, and M proteins. Cytometric analysis of cells expressing viral escape mutants possessing minimal mutations and their plasmid-expressed H, F, and M proteins indicates that immune resistance is due to particular mutations that can occur in any of these three proteins that affect at distance, rather than directly, the native conformation of the MV-H globular head and hence its epitopes. A high percentage of the escape mutants contain mutations found in cases of Subacute Sclerosing Panencephalitis (SSPE) and our results could potentially shed light on the pathogenesis of this rare fatal disease. Hasan Kweder, Michelle Ainouze, Sara Louise Cosby, Claude P. Muller, Camille Lévy, Els Verhoeyen, François-Loïc Cosset, Evelyne Manet, and Robin Buckland Copyright © 2014 Hasan Kweder et al. All rights reserved. Recent Advances in Diagnosis, Prevention, and Treatment of Human Respiratory Syncytial Virus Mon, 09 Dec 2013 09:58:27 +0000 http://www.hindawi.com/journals/av/2013/595768/ Human respiratory syncytial virus (RSV) is a common cause of respiratory infection in infants and the elderly, leading to significant morbidity and mortality. The interdisciplinary fields, especially biotechnology and nanotechnology, have facilitated the development of modern detection systems for RSV. Many anti-RSV compounds like fusion inhibitors and RNAi molecules have been successful in laboratory and clinical trials. But, currently, there are no effective drugs for RSV infection even after decades of research. Effective diagnosis can result in effective treatment, but the progress in both of these facets must be concurrent. The development in prevention and treatment measures for RSV is at appreciable pace, but the implementation into clinical practice still seems a challenge. This review attempts to present the promising diverse research approaches and advancements in the area of diagnosis, prevention, and treatment that contribute to RSV management. Swapnil Subhash Bawage, Pooja Munnilal Tiwari, Shreekumar Pillai, Vida Dennis, and Shree Ram Singh Copyright © 2013 Swapnil Subhash Bawage et al. All rights reserved. Emergence of Hepatitis B Virus Genotype F in Aligarh Region of North India Thu, 05 Dec 2013 11:09:29 +0000 http://www.hindawi.com/journals/av/2013/846849/ Introduction. HBV genotypes and subtypes are useful clinical and epidemiological markers. In this study prevalent HBV genotypes were assessed in relation to serological profile and clinical status. Material & Methods. 107 cases of HBV were genotyped. Detailed clinical history was elicited from them. HBsAg, HBeAg, anti-HBs, anti-HBe, and anti-HBc-IgM were assessed. HBV genotyping was performed using Kirschberg's type specific primers (TSP-PCR), heminested PCR, and Naito's monoplex PCR. Nucleotide sequencing was performed. Results. A total of 97 (91%) were genotyped following the methods of Kirschberg et al./Naito et al. Genotype D was by far the most prevalent genotype 91 (85.04%) in this region. A surprising finding was the detection of genotype F in 5 (4.67%) of our patients. Genotype A strangely was observed only in one case. In 85.7% genotype D was associated with moderate to severe liver disease, 43.9% HBeAg, and 18.7% anti-HBc-IgM positivity. Majority of genotype F (80%) was seen in mild to moderate liver disease. It was strongly associated with HBeAg 60% and 20% anti-HBc-IgM positivity. Conclusion. Emergence of genotype F in India merits further study regarding its clinical implications and treatment modalities. Knowledge about HBV genotypes can direct a clinician towards more informed management of HBV patients. Hiba Sami, Meher Rizvi, Mohd Azam, Rathindra M. Mukherjee, Indu Shukla, M. R. Ajmal, and Abida Malik Copyright © 2013 Hiba Sami et al. All rights reserved. Elucidating the Interacting Domains of Chandipura Virus Nucleocapsid Protein Mon, 28 Oct 2013 11:00:35 +0000 http://www.hindawi.com/journals/av/2013/594319/ The nucleocapsid (N) protein of Chandipura virus (CHPV) plays a crucial role in viral life cycle, besides being an important structural component of the virion through proper organization of its interactions with other viral proteins. In a recent study, the authors had mapped the associations among CHPV proteins and shown that N protein interacts with four of the viral proteins: N, phosphoprotein (P), matrix protein (M), and glycoprotein (G). The present study aimed to distinguish the regions of CHPV N protein responsible for its interactions with other viral proteins. In this direction, we have generated the structure of CHPV N protein by homology modeling using SWISS-MODEL workspace and Accelrys Discovery Studio client 2.55 and mapped the domains of N protein using PiSQRD. The interactions of N protein fragments with other proteins were determined by ZDOCK rigid-body docking method and validated by yeast two-hybrid and ELISA. The study revealed a unique binding site, comprising of amino acids 1–30 at the N terminus of the nucleocapsid protein (N1) that is instrumental in its interactions with N, P, M, and G proteins. It was also observed that N2 associates with N and G proteins while N3 interacts with N, P, and M proteins. Kapila Kumar, Sreejith Rajasekharan, Sahil Gulati, Jyoti Rana, Reema Gabrani, Chakresh K. Jain, Amita Gupta, Vijay K. Chaudhary, and Sanjay Gupta Copyright © 2013 Kapila Kumar et al. All rights reserved. Viruses as Modulators of Mitochondrial Functions Thu, 24 Oct 2013 11:14:16 +0000 http://www.hindawi.com/journals/av/2013/738794/ Mitochondria are multifunctional organelles with diverse roles including energy production and distribution, apoptosis, eliciting host immune response, and causing diseases and aging. Mitochondria-mediated immune responses might be an evolutionary adaptation by which mitochondria might have prevented the entry of invading microorganisms thus establishing them as an integral part of the cell. This makes them a target for all the invading pathogens including viruses. Viruses either induce or inhibit various mitochondrial processes in a highly specific manner so that they can replicate and produce progeny. Some viruses encode the Bcl2 homologues to counter the proapoptotic functions of the cellular and mitochondrial proteins. Others modulate the permeability transition pore and either prevent or induce the release of the apoptotic proteins from the mitochondria. Viruses like Herpes simplex virus 1 deplete the host mitochondrial DNA and some, like human immunodeficiency virus, hijack the host mitochondrial proteins to function fully inside the host cell. All these processes involve the participation of cellular proteins, mitochondrial proteins, and virus specific proteins. This review will summarize the strategies employed by viruses to utilize cellular mitochondria for successful multiplication and production of progeny virus. Sanjeev K. Anand and Suresh K. Tikoo Copyright © 2013 Sanjeev K. Anand and Suresh K. Tikoo. All rights reserved. Hepatitis Delta Virus: A Peculiar Virus Wed, 02 Oct 2013 11:58:58 +0000 http://www.hindawi.com/journals/av/2013/560105/ The hepatitis delta virus (HDV) is distributed worldwide and related to the most severe form of viral hepatitis. HDV is a satellite RNA virus dependent on hepatitis B surface antigens to assemble its envelope and thus form new virions and propagate infection. HDV has a small 1.7 Kb genome making it the smallest known human virus. This deceivingly simple virus has unique biological features and many aspects of its life cycle remain elusive. The present review endeavors to gather the available information on HDV epidemiology and clinical features as well as HDV biology. Carolina Alves, Cristina Branco, and Celso Cunha Copyright © 2013 Carolina Alves et al. All rights reserved. Production of Platinum Atom Nanoclusters at One End of Helical Plant Viruses Wed, 25 Sep 2013 13:10:59 +0000 http://www.hindawi.com/journals/av/2013/746796/ Platinum atom clusters (Pt nanoparticles, Pt-NPs) were produced selectively at one end of helical plant viruses, tobacco mosaic virus (TMV) and potato virus X (PVX), when platinum coordinate compounds were reduced chemically by borohydrides. Size of the platinum NPs depends on conditions of the electroless deposition of platinum atoms on the virus. Results suggest that the Pt-NPs are bound concurrently to the terminal protein subunits and the 5′ end of encapsidated TMV RNA. Thus, a special structure of tobacco mosaic virus and potato X virus particles with nanoparticles of platinum, which looks like a push-pin with platinum head and virus needle, was obtained. Similar results were obtained with ultrasonically fragmented TMV particles. By contrast, the Pt-NPs fully filled the central axial hole of in vitro assembled RNA-free TMV-like particles. We believe that the results presented here will be valuable in the fundamental understanding of interaction of viral platforms with ionic metals and in a mechanism of nanoparticles formation. Yuri Drygin, Olga Kondakova, and Joseph Atabekov Copyright © 2013 Yuri Drygin et al. All rights reserved. The Possible Role of TLR2 in Chronic Hepatitis B Patients with Precore Mutation Wed, 25 Sep 2013 09:06:12 +0000 http://www.hindawi.com/journals/av/2013/780319/ Recognition mechanisms of innate immune response help to improve immunotherapeutic strategies in HBeAg-negative chronic hepatitis B (CHB). Toll-like receptor 2 (TLR2) is an important component of innate immunity. In this study, the frequency of precore mutations of the hepatitis B virus (HBV) and serum TLR2 were evaluated in CHB patients. Fifty-one patients with chronic hepatitis B, negative for HBeAg and detectable HBV DNA, were examined for the presence of mutations in pre-core region of HBV genome by direct sequencing. Serum TLR2 was measured by enzyme-linked immunosorbent assay. Interactions of truncated HBeAg and TLR2 proteins were evaluated with molecular docking software. The G1896A pre-core mutation were detected in 29 (57%) which was significantly associated with higher concentration of serum TLR2 in comparison with patients without this mutation (4.8 2.9 versus 3.4 2.2 ng/mL, ). There was also a significant correlation between serum ALT and TLR-2 (; ). Docking results illustrated residues within the N-terminus of truncated HBeAg and TLR2, which might facilitate the interaction of these proteins. These findings showed the dominance of G1896A pre-core mutation of HBV variants in this community which was correlated with serum TLR2. Moreover TLR2 is critical for induction of inflammatory cytokines and therefore ALT elevation. Malihe Moradzadeh, Sirous Tayebi, Hossein Poustchi, Kourosh Sayehmiri, Parisa Shahnazari, Elnaz Naderi, Ghodratollah Montazeri, and Ashraf Mohamadkhani Copyright © 2013 Malihe Moradzadeh et al. All rights reserved. Recombinant Varicella-Zoster Virus Vaccines as Platforms for Expression of Foreign Antigens Thu, 13 Jun 2013 11:56:33 +0000 http://www.hindawi.com/journals/av/2013/219439/ Varicella-zoster virus (VZV) vaccines induce immunity against childhood chickenpox and against shingles in older adults. The safety, efficacy, and widespread use of VZV vaccines suggest that they may also be effective as recombinant vaccines against other infectious diseases that affect the young and the elderly. The generation of recombinant VZV vaccines and their evaluation in animal models are reviewed. The potential advantages and limitations of recombinant VZV vaccines are addressed. Wayne L. Gray Copyright © 2013 Wayne L. Gray. All rights reserved. Safety and Efficacy of Hepatitis B Vaccination in Cirrhosis of Liver Thu, 06 Jun 2013 13:15:37 +0000 http://www.hindawi.com/journals/av/2013/196704/ Introduction. Patients with chronic liver disease (CLD) are more likely to have severe morbidity and fatality rate due to superimposed acute or chronic hepatitis B (HBV) infection. The literature has shown that hepatitis B vaccines are safe and effective in patients with CLD, but the data in cirrhosis liver is lacking. We assessed the safety and immunogenicity of HBV vaccine in patients with cirrhosis liver. Methods. CTP classes A and B CLD patients negative for hepatitis B surface antigen and antibody to hepatitis B core antigen were included. All patients received three doses of hepatitis B vaccine 20 mcg intramuscularly at 0, 30, and 60 days. Anti-HBs antibody was measured after 120 days. Results. 52 patients with mean age years were studied. Response rates in CTP classes A and B were 88% and 33.3%. We observed that the alcoholic chronic liver disease had less antibody response (44%) than other causes of chronic liver disease such as cryptogenic 69% and HCV 75%. Conclusions. Patients with cirrhosis liver will have low antibody hepatitis B titers compared to general population. As the age and liver disease progress, the response rate for hepatitis B vaccination will still remain to be weaker. D. Ajith Roni, Rama Mohan Pathapati, A. Sathish Kumar, Lalit Nihal, K. Sridhar, and Sujith Tumkur Rajashekar Copyright © 2013 D. Ajith Roni et al. All rights reserved. Virus Entry by Endocytosis Sun, 21 Apr 2013 13:21:26 +0000 http://www.hindawi.com/journals/av/2013/469538/ Anthony V. Nicola, Hector C. Aguilar, Jason Mercer, Brent Ryckman, and Christopher M. Wiethoff Copyright © 2013 Anthony V. Nicola et al. All rights reserved. Erratum to “Endocytosis of Integrin-Binding Human Picornaviruses” Wed, 03 Apr 2013 17:35:37 +0000 http://www.hindawi.com/journals/av/2013/412909/ Pirjo Merilahti, Satu Koskinen, Outi Heikkilä, Eveliina Karelehto, and Petri Susi Copyright © 2013 Pirjo Merilahti et al. All rights reserved. Transmitted Drug Resistance among People Living with HIV/Aids at Major Cities of Sao Paulo State, Brazil Tue, 15 Jan 2013 11:47:53 +0000 http://www.hindawi.com/journals/av/2013/878237/ Human immunodeficiency virus type 1 (HIV-1) transmitted drug resistance (TDR) is an important public health issue. In Brazil, low to intermediate resistance levels have been described. We assessed 225 HIV-1 infected, antiretroviral naïve individuals, from HIV Reference Centers at two major metropolitan areas of Sao Paulo (Sao Paulo and Campinas), the state that concentrates most of the Brazilian Aids cases. TDR was analyzed by Stanford Calibrated Population Resistance criteria (CPR), and mutations were observed in 17 individuals (7.6%, 95% CI: 4.5%–11.9%). Seventy-six percent of genomes (13/17) with TDR carried a nonnucleoside reverse transcriptase inhibitor (NNRTI) resistance mutation, mostly K103N/S (9/13, 69%), potentially compromising the preferential first-line therapy suggested by the Brazilian HIV Treatment Guideline that recommends efavirenz-based combinations. Moreover, 6/17 (35%) had multiple mutations associated with resistance to one or more classes. HIV-1 B was the prevalent subtype (80%); other subtypes include HIV-1 F and C, mosaics BC, BF, and single cases of subtype A1 and CRF02_AG. The HIV Reference Center of Campinas presented more cases with TDR, with a significant association of TDR with clade B infection (). Joao Leandro Paula Ferreira, Rosangela Rodrigues, Andre Minhoto Lança, Valeria Correia de Almeida, Simone Queiroz Rocha, Taisa Grotta Ragazzo, Denise Lotufo Estevam, and Luis Fernando de Macedo Brigido Copyright © 2013 Joao Leandro Paula Ferreira et al. All rights reserved. Cellular Factors Implicated in Filovirus Entry Sun, 13 Jan 2013 08:57:53 +0000 http://www.hindawi.com/journals/av/2013/487585/ Although filoviral infections are still occurring in different parts of the world, there are no effective preventive or treatment strategies currently available against them. Not only do filoviruses cause a deadly infection, but they also have the potential of being used as biological weapons. This makes it imperative to comprehensively study these viruses in order to devise effective strategies to prevent the occurrence of these infections. Entry is the foremost step in the filoviral replication cycle and different studies have reported the involvement of a myriad of cellular factors including plasma membrane components, cytoskeletal proteins, endosomal components, and cytosolic factors in this process. Signaling molecules such as the TAM family of receptor tyrosine kinases comprising of Tyro3, Axl, and Mer have also been implicated as putative entry factors. Additionally, filoviruses are suggested to bind to a common receptor and recent studies have proposed T-cell immunoglobulin and mucin domain 1 (TIM-1) and Niemann-Pick C1 (NPC1) as potential receptor candidates. This paper summarizes the existing literature on filoviral entry with a special focus on cellular factors involved in this process and also highlights some fundamental questions. Future research aimed at answering these questions could be very useful in designing novel antiviral therapeutics. Suchita Bhattacharyya and Thomas J. Hope Copyright © 2013 Suchita Bhattacharyya and Thomas J. Hope. All rights reserved. Influenza A Virus Entry: Implications in Virulence and Future Therapeutics Wed, 09 Jan 2013 15:26:16 +0000 http://www.hindawi.com/journals/av/2013/121924/ Influenza A viruses have broad host tropism, being able to infect a range of hosts from wild fowl to swine to humans. This broad tropism makes highly pathogenic influenza A strains, such as H5N1, potentially dangerous to humans if they gain the ability to jump from an animal reservoir to humans. How influenza A viruses are able to jump the species barrier is incompletely understood due to the complex genetic nature of the viral surface glycoprotein, hemagglutinin, which mediates entry, combined with the virus's ability to use various receptor linkages. Current therapeutics against influenza A include those that target the uncoating process after entry as well as those that prevent viral budding. While there are therapeutics in development that target entry, currently there are none clinically available. We review here the genetics of influenza A viruses that contribute to entry tropism, how these genetic alterations may contribute to receptor usage and species tropism, as well as how novel therapeutics can be developed that target the major surface glycoprotein, hemagglutinin. Emily Rumschlag-Booms and Lijun Rong Copyright © 2013 Emily Rumschlag-Booms and Lijun Rong. All rights reserved. Virus Variability and Its Impact on HIV and Hepatitis Therapy Thu, 27 Dec 2012 07:37:53 +0000 http://www.hindawi.com/journals/av/2012/607527/ Domenico Genovese, Christoph Boesecke, Nicola Coppola, and Stefano Vella Copyright © 2012 Domenico Genovese et al. All rights reserved. Retrovirus Entry by Endocytosis and Cathepsin Proteases Thu, 06 Dec 2012 14:49:50 +0000 http://www.hindawi.com/journals/av/2012/640894/ Retroviruses include infectious agents inducing severe diseases in humans and animals. In addition, retroviruses are widely used as tools to transfer genes of interest to target cells. Understanding the entry mechanism of retroviruses contributes to developments of novel therapeutic approaches against retrovirus-induced diseases and efficient exploitation of retroviral vectors. Entry of enveloped viruses into host cell cytoplasm is achieved by fusion between the viral envelope and host cell membranes at either the cell surface or intracellular vesicles. Many animal retroviruses enter host cells through endosomes and require endosome acidification. Ecotropic murine leukemia virus entry requires cathepsin proteases activated by the endosome acidification. CD4-dependent human immunodeficiency virus (HIV) infection is thought to occur via endosomes, but endosome acidification is not necessary for the entry whereas entry of CD4-independent HIVs, which are thought to be prototypes of CD4-dependent viruses, is low pH dependent. There are several controversial results on the retroviral entry pathways. Because endocytosis and endosome acidification are complicatedly controlled by cellular mechanisms, the retrovirus entry pathways may be different in different cell lines. Yoshinao Kubo, Hideki Hayashi, Toshifumi Matsuyama, Hironori Sato, and Naoki Yamamoto Copyright © 2012 Yoshinao Kubo et al. All rights reserved. Endocytosis of Integrin-Binding Human Picornaviruses Tue, 27 Nov 2012 15:11:08 +0000 http://www.hindawi.com/journals/av/2012/547530/ Picornaviruses that infect humans form one of the largest virus groups with almost three hundred virus types. They include significant enteroviral pathogens such as rhino-, polio-, echo-, and coxsackieviruses and human parechoviruses that cause wide range of disease symptoms. Despite the economic importance of picornaviruses, there are no antivirals. More than ten cellular receptors are known to participate in picornavirus infection, but experimental evidence of their role in cellular infection has been shown for only about twenty picornavirus types. Three enterovirus types and one parechovirus have experimentally been shown to bind and use integrin receptors in cellular infection. These include coxsackievirus A9 (CV-A9), echovirus 9, and human parechovirus 1 that are among the most common and epidemic human picornaviruses and bind to αV-integrins via RGD motif that resides on virus capsid. In contrast, echovirus 1 (E-1) has no RGD and uses integrin α2β1 as cellular receptor. Endocytosis of CV-A9 has recently been shown to occur via a novel Arf6- and dynamin-dependent pathways, while, contrary to collagen binding, E-1 binds inactive β1 integrin and enters via macropinocytosis. In this paper, we review what is known about receptors and endocytosis of integrin-binding human picornaviruses. Pirjo Merilahti, Satu Koskinen, Outi Heikkilä, Eveliina Karelehto, and Petri Susi Copyright © 2012 Pirjo Merilahti et al. All rights reserved. Productive Entry Pathways of Human Rhinoviruses Mon, 26 Nov 2012 08:26:08 +0000 http://www.hindawi.com/journals/av/2012/826301/ Currently, complete or partial genome sequences of more than 150 human rhinovirus (HRV) isolates are known. Twelve species A use members of the low-density lipoprotein receptor family for cell entry, whereas the remaining HRV-A and all HRV-B bind ICAM-1. HRV-Cs exploit an unknown receptor. At least all A and B type viruses depend on receptor-mediated endocytosis for infection. In HeLa cells, they are internalized mainly by a clathrin- and dynamin-dependent mechanism. Upon uptake into acidic compartments, the icosahedral HRV capsid expands by ~4% and holes open at the 2-fold axes, close to the pseudo-3-fold axes and at the base of the star-shaped dome protruding at the vertices. RNA-protein interactions are broken and new ones are established, the small internal myristoylated capsid protein VP4 is expelled, and amphipathic N-terminal sequences of VP1 become exposed. The now hydrophobic subviral particle attaches to the inner surface of endosomes and transfers its genomic (+) ssRNA into the cytosol. The RNA leaves the virus starting with the poly(A) tail at its 3′-end and passes through a membrane pore contiguous with one of the holes in the capsid wall. Alternatively, the endosome is disrupted and the RNA freely diffuses into the cytoplasm. Renate Fuchs and Dieter Blaas Copyright © 2012 Renate Fuchs and Dieter Blaas. All rights reserved. Immunopathogenic and Neurological Mechanisms of Canine Distemper Virus Sun, 04 Nov 2012 08:25:52 +0000 http://www.hindawi.com/journals/av/2012/163860/ Canine distemper is a highly contagious viral disease caused by the canine distemper virus (CDV), which is a member of the Morbillivirus genus, Paramyxoviridae family. Animals that most commonly suffer from this disease belong to the Canidae family; however, the spectrum of natural hosts for CDV also includes several other families of the order Carnivora. The infectious disease presents worldwide distribution and maintains a high incidence and high levels of lethality, despite the availability of effective vaccines, and no specific treatment. CDV infection in dogs is characterized by the presentation of systemic and/or neurological courses, and viral persistence in some organs, including the central nervous system (CNS) and lymphoid tissues. An elucidation of the pathogenic mechanisms involved in canine distemper disease will lead to a better understanding of the injuries and clinical manifestations caused by CDV. Ultimately, further insight about this disease will enable the improvement of diagnostic methods as well as therapeutic studies. Otávio Valério Carvalho, Clarisse Vieira Botelho, Caroline Gracielle Torres Ferreira, Paulo Oldemar Scherer, Jamária Adriana Pinheiro Soares-Martins, Márcia Rogéria Almeida, and Abelardo Silva Júnior Copyright © 2012 Otávio Valério Carvalho et al. All rights reserved. Features of Human Herpesvirus-6A and -6B Entry Tue, 23 Oct 2012 08:45:23 +0000 http://www.hindawi.com/journals/av/2012/384069/ Human herpesvirus-6 (HHV-6) is a T lymphotropic herpesvirus belonging to the Betaherpesvirinae subfamily. HHV-6 was long classified into variants A and B (HHV-6A and HHV-6B); however, recently, HHV-6A and HHV-6B were reclassified as different species. The process of herpesvirus entry into target cells is complicated, and in the case of HHV-6A and HHV-6B, the detailed mechanism remains to be elucidated, although both viruses are known to enter cells via endocytosis. In this paper, (1) findings about the cellular receptor and its ligand for HHV-6A and HHV-6B are summarized, and (2) a schematic model of HHV-6A’s replication cycle, including its entry, is presented. In addition, (3) reports showing the importance of lipids in both the HHV-6A envelope and target-cell membrane for viral entry are reviewed, and (4) glycoproteins involved in cell fusion are discussed. Takahiro Maeki and Yasuko Mori Copyright © 2012 Takahiro Maeki and Yasuko Mori. All rights reserved. Virus Immune Evasion: New Mechanism and Implications in Disease Outcome Mon, 24 Sep 2012 14:00:18 +0000 http://www.hindawi.com/journals/av/2012/490549/ Rika Draenert, John Frater, and Julia G. Prado Copyright © 2012 Rika Draenert et al. All rights reserved. Viral Infection: An Evolving Insight into the Signal Transduction Pathways Responsible for the Innate Immune Response Tue, 11 Sep 2012 15:40:58 +0000 http://www.hindawi.com/journals/av/2012/131457/ The innate immune response is initiated by the interaction of stereotypical pathogen components with genetically conserved receptors for extracytosolic pathogen-associated molecular patterns (PAMPs) or intracytosolic nucleic acids. In multicellular organisms, this interaction typically clusters signal transduction molecules and leads to their activations, thereby initiating signals that activate innate immune effector mechanisms to protect the host. In some cases programmed cell death—a fundamental form of innate immunity—is initiated in response to genotoxic or biochemical stress that is associated with viral infection. In this paper we will summarize innate immune mechanisms that are relevant to viral pathogenesis and outline the continuing evolution of viral mechanisms that suppress the innate immunity in mammalian hosts. These mechanisms of viral innate immune evasion provide significant insight into the pathways of the antiviral innate immune response of many organisms. Examples of relevant mammalian innate immune defenses host defenses include signaling to interferon and cytokine response pathways as well as signaling to the inflammasome. Understanding which viral innate immune evasion mechanisms are linked to pathogenesis may translate into therapies and vaccines that are truly effective in eliminating the morbidity and mortality associated with viral infections in individuals. Girish J. Kotwal, Steven Hatch, and William L. Marshall Copyright © 2012 Girish J. Kotwal et al. All rights reserved. Elevated VEGF Levels in Pulmonary Edema Fluid and PBMCs from Patients with Acute Hantavirus Pulmonary Syndrome Wed, 22 Aug 2012 08:52:19 +0000 http://www.hindawi.com/journals/av/2012/674360/ Hantavirus pulmonary syndrome is characterized by vascular permeability, hypoxia, and acute pulmonary edema. Vascular endothelial growth factor (VEGF) is induced by hypoxia, potently induces vascular permeability, and is associated with high-altitude-induced pulmonary edema. Hantaviruses alter the normal regulation of β3 integrins that restrict VEGF-directed permeability and hantavirus infected endothelial cells are hyperresponsive to the permeabilizing effects of VEGF. However, the role of VEGF in acute pulmonary edema observed in HPS patients remains unclear. Here we retrospectively evaluate VEGF levels in pulmonary edema fluid (PEF), plasma, sera, and PBMCs from 31 HPS patients. VEGF was elevated in HPS patients PEF compared to controls with the highest levels observed in PEF samples from a fatal HPS case. VEGF levels were highest in PBMC samples during the first five days of hospitalization and diminished during recovery. Significantly increased PEF and PBMC VEGF levels are consistent with acute pulmonary edema observed in HPS patients and HPS disease severity. We observed substantially lower VEGF levels in a severe HPS disease survivor after extracorporeal membrane oxygenation. These findings suggest the importance of patients’ VEGF levels during HPS, support the involvement of VEGF responses in HPS pathogenesis, and suggest targeting VEGF responses as a potential therapeutic approach. Irina Gavrilovskaya, Elena Gorbunova, Frederick Koster, and Erich Mackow Copyright © 2012 Irina Gavrilovskaya et al. All rights reserved. Roles for Endothelial Cells in Dengue Virus Infection Thu, 16 Aug 2012 09:37:08 +0000 http://www.hindawi.com/journals/av/2012/840654/ Dengue viruses cause two severe diseases that alter vascular fluid barrier functions, dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS). The endothelium is the primary fluid barrier of the vasculature and ultimately the effects of dengue virus infection that cause capillary leakage impact endothelial cell (EC) barrier functions. The ability of dengue virus to infect the endothelium provides a direct means for dengue to alter capillary permeability, permit virus replication, and induce responses that recruit immune cells to the endothelium. Recent studies focused on dengue virus infection of primary ECs have demonstrated that ECs are efficiently infected, rapidly produce viral progeny, and elicit immune enhancing cytokine responses that may contribute to pathogenesis. Furthermore, infected ECs have also been implicated in enhancing viremia and immunopathogenesis within murine dengue disease models. Thus dengue-infected ECs have the potential to directly contribute to immune enhancement, capillary permeability, viremia, and immune targeting of the endothelium. These effects implicate responses of the infected endothelium in dengue pathogenesis and rationalize therapeutic targeting of the endothelium and EC responses as a means of reducing the severity of dengue virus disease. Nadine A. Dalrymple and Erich R. Mackow Copyright © 2012 Nadine A. Dalrymple and Erich R. Mackow. All rights reserved. Association of Active Human Herpesvirus-6, -7 and Parvovirus B19 Infection with Clinical Outcomes in Patients with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Mon, 13 Aug 2012 12:55:02 +0000 http://www.hindawi.com/journals/av/2012/205085/ Frequency of active human herpesvirus-6, -7 (HHV-6, HHV-7) and parvovirus B19 (B19) infection/coinfection and its association with clinical course of ME/CFS was evaluated. 108 ME/CFS patients and 90 practically healthy persons were enrolled in the study. Viral genomic sequences were detected by PCR, virus-specific antibodies and cytokine levels—by ELISA, HHV-6 variants—by restriction analysis. Active viral infection including concurrent infection was found in 64.8% (70/108) of patients and in 13.3% (12/90) of practically healthy persons. Increase in peripheral blood leukocyte DNA HHV-6 load as well as in proinflammatory cytokines' levels was detected in patients during active viral infection. Definite relationship was observed between active betaherpesvirus infection and subfebrility, lymphadenopathy and malaise after exertion, and between active B19 infection and multijoint pain. Neuropsychological disturbances were detected in all patients. The manifestation of symptoms was of more frequent occurrence in patients with concurrent infection. The high rate of active HHV-6, HHV-7 and B19 infection/coinfection with the simultaneous increase in plasma proinflammatory cytokines' level as well as the association between active viral infection and distinctive types of clinical symptoms shows necessity of simultaneous study of these viral infections for identification of possible subsets of ME/CFS. Svetlana Chapenko, Angelika Krumina, Inara Logina, Santa Rasa, Maksims Chistjakovs, Alina Sultanova, Ludmila Viksna, and Modra Murovska Copyright © 2012 Svetlana Chapenko et al. All rights reserved.