Here a virus, there a virus, everywhere the same virus?

There are an estimated 10(31) viruses on Earth, most of which are phages that infect bacteria. Metagenomic analyses have shown that environmental viral communities are incredibly diverse. There are an estimated 5000 viral genotypes in 200 liters of seawater and possibly a million different viral genotypes in one kilogram of marine sediment. By contrast, some culturing and molecular studies have found that viruses move between different biomes. Together, these findings suggest that viral diversity could be high on a local scale but relatively limited globally. Also, by moving between environments, viruses can facilitate horizontal gene transfer.     

How does a virus bud?

How does a virus bud from the plasma membrane of its host? Here we investigate several possible rate-limiting processes, including thermal fluctuations of the plasma membrane, hydrodynamic interactions, and diffusion of the glycoprotein spikes. We find that for bending moduli greater than 3 x 10(-13) ergs, membrane thermal fluctuations are insufficient to wrap the viral capsid, and the mechanical force driving the budding process must arise from some other process. If budding is limited by the rate at which glycoprotein spikes can diffuse to the budding site, we compute that the budding time is 10-20 min, in accord with the experimentally determined upper limit of 20 min. In light of this, we suggest some alternative mechanisms for budding and provide a rationale for the observation that budding frequently occurs in regions of high membrane curvature.     

Is parainfluenza virus a threatening virus for human cancer cell lines?

Immortalized cell lines, such as human cancer cell lines, are an indispensable experimental resource for many types of biological and medical research. However, unless the cell line has been authenticated prior to use, interpretation of experimental results may be problematic. The potential problems this may cause are illustrated by studies in which authentication of cell lines has not been carried out. For example, immortalized cell lines may unknowingly be infected with viruses that alter their characteristics. In fact, parainfluenza virus type 5 (PIV5) poses a threat to the use of immortalized cell lines in biological and medical research; PIV5 infection significantly alters cellular physiology associated with the response to interferon. If PIV5 infection is widespread in immortalized cell lines, then a very large number of published studies might have to be re-evaluated. Fortunately, analyses of a large number of immortalized cell lines indicate that PIV5 infection is not widespread.     

Founder virus population related to route of virus transmission: a determinant of intrahost human immunodeficiency virus type 1 evolution?

We and others have shown that in individual human immunodeficiency virus type 1 (HIV-1) infection, the adaptive evolution of HIV-1 is influenced by host immune competence. In this study, we tested the hypothesis that in addition to selective forces operating within the host, transmission bottlenecks have an impact on HIV-1 intrahost evolution. Therefore, we studied the intrahost evolution of the V3 region of the external glycoprotein gp120 of HIV-1 during the 3- and 5-year periods following seroconversion after parenteral versus sexual (male-to-male) transmission in 41 participants of the Amsterdam prospective cohorts of homosexual men (n = 31) and intravenous drug users (IVDUs; n = 10) who were AIDS free and had comparable numbers of CD4+ cells. We observed that HIV-1 strains in homosexual men accumulated over 5 years more nonsynonymous substitutions within the V3 loop than HIV-1 strains in IVDUs as a result of lower rates of nonsynonymous evolution in both the initial 3-year period from seroconversion and the following 2-year period as well as a larger proportion of nonsynonymous back substitutions in IVDUs. The mean numbers of synonymous substitutions did not differ between the two risk groups. Since HIV-1 strains in IVDUs could be distinguished from the viruses of homosexual men based on several nucleotide substitutions of which the most conserved is a synonymous substitution at the tip of the V3 loop (GGC pattern), we studied whether the founder virus population itself has an impact on the intrahost evolution of HIV-1. The mean number of nonsynonymous substitutions accumulated over 5 years within the V3 loop was lower in 10 IVDUs infected by the HIV-1 strains with the GGC signature than in 4 IVDUs infected by HIV-1 strains lacking this pattern, while the mean numbers of synonymous substitutions were similar in the two groups.     

Is gibbon ape leukaemia virus still a threat?

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Is there a role for actin in virus budding?

Electrophoretic data from both sodium dodecyl sulfate-polyacrylamide gels (SDS-PAGE) and acid-urea gels reveal a protein in purified murine mammary tumor virus (MuMTV) which co-migrates with purified chick skeletal muscle actin. 125I-labeling of intact and disrupted virus preparations shows that the actin-like protein is not artifactually adsorbed to the outside of virions during isolation. Quantitative SDS- PAGE and examination of negatively stained preparations show that the actin cannot be accounted for by a contaminating population of virus- free vesicles. The ultrastructure of mammary epithelial cells and of Rous sarcoma virus-transformed chick embryo fibroblasts shows that virus extrusion is associated with filament-containing cellular processes. In particular, MuMTV is released from the ends of long microvilli which contain a bundle of 6-8-nm microfilaments and share other structural features with intestinal microvilli. We suggest that virus nucleoids require an interaction with host cell contractile proteins for their extrusion from the cell.     

Antiviral activity of 3,4’-dihydroxyflavone on influenza a virus

Influenza virus infection causes thousands of deaths and millions of hospitalizations worldwide every year and the emergence of resistance to anti-influenza drugs has prompted scientists to seek new natural antiviral materials. In this study, we screened 13 different flavonoids from various flavonoid groups to identify the most potent antiviral flavonoid against human influenza A/PR/8/34 (H1N1). The 3-hydroxyl group flavonoids, including 3,2?dihydroxyflavone (3,2?DHF) and 3,4?dihydroxyflavone (3,4?DHF), showed potent anti-influenza activity. They inhibited viral neuraminidase activity and viral adsorption onto cells. To confirm the anti-influenza activity of these flavonoids, we used an in vivo mouse model. In mice infected with human influenza, oral administration of 3,4?DHF significantly decreased virus titers and pathological changes in the lung and reduced body weight loss and death. Our data suggest that 3-hydroxyl group flavonoids, particularly 3,4?DHF, have potent antiviral activity against human influenza A/PR/8/34 (H1N1) in vitro and in vivo. Further clinical studies are needed to investigate the therapeutic and prophylactic potential of the 3-hydroxyl group flavonoids in treating influenza pandemics.     

Adeno-associated virus: a key to the human genome?

Adeno-associated viruses (AAV) are widely spread throughout the human population, yet no pathology has been associated with infection. This fact, together with the availability of simple molecular techniques to alter the packaged viral genome, has made AAV a serious contender in the search for an ideal gene therapy delivery vehicle. However, our understanding of the intriguing features of this virus is far from exhausted and it is likely that the mechanisms underlying the viral lifestyle will reveal possible novel strategies that can be employed in future clinical approaches. One such aspect is the unique approach AAV has evolved in order to establish latency. In the absence of a cellular milieu that will support productive viral replication, wild-type AAV can integrate its genome site specifically into a locus on human chromosome 19 (termed AAVS1), where it resides without apparent effects on the host cell until cellular conditions are changed by outside influences, such as adenovirus super-infection, which will lead to the rescue of the viral genome and productive replication. This article will introduce the biology of AAV, the unique viral strategy of targeted genome integration and address relevant questions within the context of attempts to establish therapeutic approaches that will utilize targeted gene addition to the human genome.     

Measles virus: a future therapeutic agent in oncology?

Measles is a potential lethal disease, justifying large immunization campaigns. Attenuated strains are used in immunization with very good safety records. Interestingly, following clinical observations of tumor regressions after measles infection, preclinical and clinical studies have highlighted the therapeutic potential of attenuated strains of measles. The aim of this review is to explain how these viruses can selectively infect and kill cancer cells, and how this selectivity can be improved. We will detail the therapeutic strategies under development, in particular the combination of viruses with chemotherapy and radiation therapy. Furthermore, the engineering of measles viruses encoding the sodium/iodide symporter could enable virus-directed radio-isotope therapy. Antiviral immunity could be a limit of measles therapy. We will highlight the promising combinations with immunosuppressive drugs and innovative strategies using infected cell carriers, aiming at circumventing the immune response and paving the way to future clinical trials.     

Do corticosteroids have a role in treating Ebola virus disease?

<正>Dear Editor,Humans have been fighting Ebola virus disease(EVD)since its first outbreak in 1976 in Yambuku village in the Democratic Republic of the Congo(previously Zaire).EVD is part of the Filoviridae family of viruses that includes Ebola and Marburg viruses.To date,EVD,one of the most deadly communicable diseases known to humans,has had15 outbreaks in Africa.In 2014,the most severe and complicated outbreak yet swept through the West African countries of Guinea,Liberia,Nigeria,Senegal and Sierra Leone,     

Epstein-Barr virus and rheumatoid arthritis: is there a link?

Rheumatoid arthritis is a systemic autoimmune disease characterized by chronic, destructive, debilitating arthritis. Its etiology is unknown; it is presumed that environmental factors trigger development in the genetically predisposed. Epstein-Barr virus, a nearly ubiquitous virus in the human population, has generated great interest as a potential trigger. This virus stimulates polyclonal lymphocyte expansion and persists within B lymphocytes for the host's life, inhibited from reactivating by the immune response. In latent and replicating forms, it has immunomodulating actions that could play a role in the development of this autoimmune disease. The evidence linking Epstein-Barr virus and rheumatoid arthritis is reviewed.     

The Leeuwenhoek Lecture, 1980. Is it a virus?

It was shown many years ago that viruses can cause common cold but it is often forgotten that there were prolonged investigations and disagreements before this was agreed. It wa difficult to detect or propagate any virus in the laboratory and it has taken more than two decades of research to arrive at a reasonably complete list of the viruses that cause colds and related diseases. To do so, new techniques were developed by which these very specialized viruses can be grown and studied. Nevertheless unanswered questions remain on the relation between them and the diseases. This research has required finding answers to several different questions about the viruses and the diseases. The questions cannot all be answered in the same way for all virus infections, and recent research has shown that we can learn a great deal about certain viruses and diseases without answering all of the questions; for instance, the role of rotaviruses in diarrhoea was established though the viruses could not be effectively grown in the laboratory. In the light of these ideas I shall refer to the evidence that mental diseases may be due to virus infections and the recent finding that cerebrospinal fluid from such patients produced a cytopathic effect in tissue cultures that was apparently due to a virus-like agent.     

GB virus-C/hepatitis G virus infection in Taiwan: A virus that fails to cause a disease?

Recently, an RNA virus designated GB virus-C or hepatitis G virus (GBV-C/HGV) was identified; however, its clinical significance remains uncertain. This discovery prompted us to investigate the virological, epidemiological and clinical implications of GBV-C/HGV infection in Taiwan where chronic liver diseases and liver cancer are endemic. Our results showed that genetic heterogeneity of GBV-C/HGV isolates exists, and primers from the highly conserved 5 untranslated region of viral genome can efficiently detect GBV-C/HGV RNA. Epidemiological surveys showed that GBV-C/HGV infection is common in high-risk groups in Taiwan, and its coinfection does not aggravate the course of chronic hepatitis B or C. A prospective study of transfusion-transmitted GBV-C/HGV infection also showed GBV-C/HGV does not cause classic hepatitis in most patients. In addition, GBV-C/HGV plays a minimal role in causing fulminant hepatitis. Like hepatitis C virus, sexual transmission of GBV-C/HGV exists. The risk increases with prolonged duration of exposure. In addition, high-titered maternal viremia and mode of delivery are associated with the mother-to-infant transmission of GBV-C/HGV. Interestingly, we found that GBV-C/HGV exerts no suppression on levels of chronic hepatitis B or hepatitis C viremia, and GBV-C/HGV responds to interferon; however, ribavirin plus interferon does not induce a higher sustained response. As to the replication sites of GBV-C/HGV, our preliminary results showed liver and peripheral blood mononuclear cells are not the major sites for GBV-C/HGV replication, and thus GBV-C/HGV is not a primary hepatotropic virus. In conclusion, transfusion and exchange of body fluids indeed can transmit GBV-C/HGV; however, current lines of evidence suggest that GBV-C/HGV fails to cause a disease.     

Vesicular stomatitis virus mRNA and inhibition of translation of cellular mRNA--is there a P function in vesicular stomatitis virus?

Infection of animal cells by vesicular stomatitis virus (VSV) results in inhibition of translation of cellular mRNA. We showed previously that, in BHK cells infected by the Glasgow isolate of VSV Indiana, this is due to competition during the initiation step of protein synthesis of viral and cellular mRNA for a constant, limiting number of ribosomes. We show here that infection of the same cells with the San Juan isolate of VSV resulted in a more rapid shutoff of host protein synthesis and that this was paralleled by a more rapid accumulation of viral mRNA. Extending our conclusion that shutoff is due to mRNA competition, we show further that the average size of polysomes translating viral and cellular mRNA was threefold smaller in cells infected by VSV San Juan than by VSV Glasgow, which, in turn, was about one-half that of uninfected cells. In all cases, cellular and viral mRNA's which encoded the same-sized polypeptides were found on the same-sized polysomes, a result indicating that the efficiency of translation of both types of mRNA's is about the same in the infected cell. Also, there was no preferential sequestration of viral or cellular mRNA's in ribonucleoprotein particles. Additional correlations between the levels of viral mRNA's and the inhibition of protein synthesis came from studies of three other wild-type VSV strains and also from studies with Vero and L cells. In particular, the rate of shutoff of L-cell protein synthesis after infection by any VSV isolate was slower than that in BHK cells, and this was correlated with a slower rate of accumulation of viral mRNA. VSV temperature-sensitive mutants which synthesized, at the nonper-missive temperature, no VSV mRNA failed to inhibit synthesis of cellular proteins. Stanners and co-workers (C. P. Stanners, A. M. Francoeur, and T. Lam, Cell 11:273-281, 1977) claimed that VSV mutant R1 inhibited synthesis of L cell protein synthesis less rapidly than did its parent wild-type strain HR. They concluded that this effect was due to a mutation in an unspecified VSV protein, “P.” We found, in both L and BHK cells, that R1 infection resulted in a slightly slower inhibition of cellular mRNA translation than did HR infection and that this was correlated with a slightly reduced accumulation of VSV mRNA. The level of VSV mRNA, rather than any specific VSV protein, appeared to be the key factor in determining the rate of shutoff of host protein synthesis.     

Complete genome sequence of a novel hantavirus variant of Rio Mamoré virus, Maripa virus, from French Guiana

We report the first complete genome sequence of Maripa virus identified in 2009 from a patient with hantavirus pulmonary syndrome in French Guiana. Maripa virus corresponds to a new variant of the Rio Mamoré virus species in the Bunyaviridae family, genus Hantavirus.     

Natural simian immunodeficiency virus transmission in mandrills: a family affair?

Understanding how pathogens spread and persist in the ecosystem is critical for deciphering the epidemiology of diseases of significance for global health and the fundamental mechanisms involved in the evolution of virulence and host resistance. Combining long-term behavioural and epidemiological data collected in a naturally infected mandrill population and a Bayesian framework, the present study investigated unknown aspects of the eco-epidemiology of simian immunodeficiency virus (SIV), the recent ancestor of HIV. Results show that, in contrast to what is expected from aggressive and sexual transmission (i.e. the two commonly accepted transmission modes for SIV), cases of SIVmnd-1 subtype were significantly correlated among related individuals (greater than 30% of the observed cases). Challenging the traditional view of SIV, this finding suggests the inheritance of genetic determinants of susceptibility to SIV and/or a role for behavioural interactions among maternal kin affecting the transmission of the virus, which would highlight the underappreciated role of sociality in the spread of infectious diseases. Outcomes of this study also provide novel insights into the role of host social structure in the evolution of pathogens.