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[Electron microscopic study of the sera of hepatitis B surface antigen (HBs Ag) subjects (author's transl)].

Electron microscopic observation of sera from 59 subjects(HBs Ag-negative controls, HBs Ag-positive asymptomatic blood donors, and HBs Ag-positive patients with acute viral hepatitis, chronic persistant or active hepatitis and alcohol-induced liver damage) was capable of specifying the morphology of the HB virus (spherical particles, rod-shaped particles and Dane particles) and of correlating the aspect of the observed viral material with the nature and evolution of the liver damage. The viral particles are observed in small amounts in asymptomatic blood donors and in patients with acute viral hepatitis, but are present in very significant quantities in chronic hepatitis. Dane particles and viral particle aggregates are more numerous in chronic active hepatitis than in chronic persistant hepatitis. The detection of HBeAg in the serum, especially found in chronic active hepatitis, correlates with the presence of Dane particles. In most cases, the observed viral particle aggregates do not seem to be associated with an immunological process.

Acute Disease↗

[Herpesvirus infection: from the primary oral lesion to recurrent herpes].

This paper presents an overview of the clinical conditions associated with a herpetic lesion at the time of the primary infection, as a true primary infection or a first herpetic accident, or during recurrences. The virus responsible, its anatomy and its functioning are detailed. The etiology and transmission of herpetic viral infection, its evolution and complications, as well as diagnostic aids are also discussed. To complete the discussion of this chronic disease which can cause acute annoyances treatment, particularly for children is reviewed, and suggestions are made to prevent it.

Acyclovir↗

[Evaluation of liver biopsies in chronic hepatitis].

New knowledge of the different hepatitis viruses and of the evolution of chronic viral hepatitis has necessitated review of the nomenclature of chronic hepatitis and of its histological categories. Some hepatologists now prefer to use a primarily aetiological classification, supplemented by histological data. The latter may be expressed in semiquantitative terms, which helps in the assessment of new therapies.

Biopsy↗

Papilloma viruses, warts, carcinoma and Langerhans cells.

In human papillomavirus (HPV) infections, Langerhans cells (LC) are essential in the control of viral infection. The evolution of HPV-derived lesions in the normal population and in graft patients is drastically different, since a high proportion of papillomas progress towards malignancy in transplant recipients. We analyzed the distribution of markers of LC and T lymphocytes, the level of keratinocyte activation and the prevalence of HPV in a series of epithelial lesions obtained from the normal population and from graft patients. The local immune response of warts, condyloma acuminata, Bowen, basal and squamous cell carcinomas (SCC) showed a moderate to intense inflammatory reaction of HLA-DR positive cells, the intensity of the immune reaction being correlated with the degree of malignancy. In the normal population, CD4-positive cells were mainly overexpressed in the dermal infiltrate of condyloma and malignant lesions, whereas in grafted patients such infiltrates were CD4- and CD8-positive without significant predominance of a single T cell subset. The epidermis of most lesions was characterized by a reduced number of CD1a-positive LC with an altered morphology. This was concomitant with the decrease or loss of beta 2-microglobulin by epithelial cells. HLA-DR antigen was sometimes expressed by keratinocytes in genital lesions and SCC from the normal population but has not been detected in immunosuppressed patients. Whereas in the normal population HPV infection was only detected in benign papillomas, both benign and oncogenic HPV DNA may be present in carcinomas from graft patients.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Heterologous RNA replication enhancer stimulates in vitro RNA synthesis and template-switching by the carmovirus, but not by the tombusvirus, RNA-dependent RNA polymerase: implication for modular evolution of RNA viruses.

The viral RNA plays multiple roles during replication of RNA viruses, serving as a template for complementary RNA synthesis and facilitating the assembly of the viral replicase complex. These roles are coordinated by cis-acting regulatory elements, such as promoters and replication enhancers (REN). To test if these RNA elements can be used by related viral RNA-dependent RNA polymerases (RdRp), we compared the potential stimulatory effects of homologous and heterologous REN elements on complementary RNA synthesis and template-switching by the tombus- (Cucumber necrosis virus, CNV), carmovirus (Turnip crinkle virus, TCV) and hepatitis C virus (HCV) RdRps in vitro. The CNV RdRp selectively utilized its cognate REN, while discriminating against the heterologous TCV REN. On the contrary, RNA synthesis by the TCV RdRp was stimulated by the TCV REN and the heterologous tombusvirus REN with comparable efficiency. The heterologous REN elements also promoted in vitro template-switching by the TCV and HCV RdRps. Based on these observations, we propose that REN elements could facilitate intervirus recombination and post-recombinational amplification of new recombinant viruses.

Base Sequence↗

Replication rate and evolution in the human immunodeficiency virus.

Population genetic and virological methods yield estimates for the mean replication rate of the Human Immunodeficiency Virus type 1 (HIV-1) that differ by six fold. I present a simple model that can reconcile the estimates obtained from each method by considering the role of intra-host population structure on viral dynamics. The model shows how latently infected cells, which may produce only a small fraction of infective viruses, can nonetheless have an important influence on estimates of mean replication rate. This contribution of latently infected cells is most important when considering the evolution of HIV and the clinical consequences of viral evolution.

Biological Evolution↗

Restrictions to RNA virus adaptation: an experimental approach.

Some basic properties of RNA viruses are their high mutation rate, their enormous population sizes and their short generation time. These properties allow RNA virus populations to quickly explore fitness landscapes. A great adaptability has been amply demonstrated in experimental, as well as in natural, populations of RNA viruses. However, at least from a theoretical point of view, a limit to the extent of viral adaptation may exist as a consequence of adaptive trade-offs arising during evolution in changing environmental conditions. Here, I review previously published results searching for such fitness trade-offs. The following scenario has been explored: the cost of host-range expansion, the cost of resistance to antiviral drugs, and the adaptation to different population densities. Despite the environmental conditions tested, results show a common pattern: whenever a virus adapt to a simple environmental situation it pays a cost in terms of adaptation to alternative situations. However, in those cases where the virus has been simultaneously adapted to different environmental conditions, this cost disappears or, at least, is greatly reduced. Finally, and as another factor imposing a limit to their speed of adaptation, I review results showing that clonal interference also plays an important role during viral evolution.

Adaptation, Physiological↗

Immune responses to myxoma virus.

Myxoma virus causes the systemic disease myxomatosis in the European rabbit (Oryctolagus cuniculus). Originating in the South American rabbit Sylvilagus brasiliensis, where it causes a relatively localized fibroma, myxoma virus is a classic example of a virus that has jumped species to produce an exotic disease and then coevolved with its new host. Like other poxviruses, myxoma virus encodes multiple proteins capable of downregulating the host innate and acquired immune responses. Other virus-encoded proteins enable replication in host lymphocytes and monocytes, for example, by inhibiting apoptosis. Detailed studies on these proteins have demonstrated novel methods of interactions with the host immune system and added substantially to the understanding of the interaction of large DNA viruses with their hosts. Despite the increasingly detailed molecular knowledge of myxoma virus, relatively little is known about the dynamics of the interaction of the virus with the integrated host-immune system during infection and, in particular, about the evolution of resistance to the virus in wild rabbits or the species barrier. This review will focus on the detailed molecular studies that have been done with myxoma virus and discuss the more limited knowledge of the pathogenesis of myxoma virus in rabbits and the ways that the consolidated immune responses may determine genetic resistance to myxomatosis.

Animals↗

A study of the evolution of coxsackievirus A24 variant in Ghana by viral RNA fingerprinting analysis.

An epidemic of acute haemorrhagic conjunctivitis (AHC) caused by coxsackievirus A24 variant (CA24v) was reported in Accra, Ghana in May 1987. We studied 7 of the viral strains collected from May to November, 1987, by RNA genome fingerprinting. Pairwise comparisons of the oligonucleotide maps showed that genetic similarity among them ranged from between 60.0 to 84.7%. Using base sequence variations deduced from genetic similarity among the isolates, isolation time of the strains and the rate of nucleotide substitution (estimated in a previous paper, Miyamura et al., 1990), we calculated divergence times and constructed a phylogenetic tree. This tree indicated that all the 7 strains had diverged from each other from 11 to 26 months before the AHC epidemic in Accra. CA24v may have been introduced into the country or the neighbouring area, at least, more than two years earlier, i.e. in the early half of 1985.

Adult↗

Treatment of Primary HIV.

Primary HIV-1 infection refers to the events surrounding the acquisition of HIV-1 infection. It is commonly associated with a nonspecific clinical syndrome that occurs within 2 to 4 weeks after exposure in 40% to 90% of persons acquiring HIV-1. Patients identified prior to seroconversion often have plasma titers in excess of 500,000 copies/mL. Over time, plasma HIV-1 RNA titers decrease and eventually reach a "set point." Treatment of primary HIV-1 infection with highly active antiretroviral therapy does not prevent establishment of chronic infection. However, it potentially may decrease the viral set point, prevent evolution of resistant mutants, preserve immune function, improve clinical outcome, and possibly allow for viral control after withdrawal of antiretroviral therapy. Transmission of viral strains with decreased susceptibility to antiviral drugs increases the difficulty of choosing an antiretroviral regimen. Other medications, including immunomodulators, are under study as adjuvant therapy for treatment of primary HIV-1 infection.

Journal Article↗

What does the molecular structure of viruses tell us about viral functions?

The structures of the protein shell of a number of simple icosahedral RNA plant and animal viruses are now known at atomic resolution. In addition, components of viral capsids such as the haemagglutinin and neuraminidase spikes of influenza virus and the hexon unit of adenovirus are known in similar detail. These structures have provided a wealth of information on viral assembly, viral disassembly, the antigenic surface on viruses available to neutralizing antibodies, the host cell receptor attachment site, fusion of viral particles with the host cell, processing of polyproteins during maturation and the manner in which antiviral agents can interfere with the function of a viral capsid.

Antibodies, Viral↗

Evolution of human influenza A viruses in nature: sequential mutations in the genomes of new H1N1.

The genetic variation of the new pandemic H1N1 influenza A viruses isolated in 1977 was analyzed by two-dimensional oligonucleotide fingerprinting and RNA sequencing. Differences were observed in the fingerprints of the RNAs of these viruses, and analysis of the changes suggested that sequential mutations occurred in their genomes. Based on these data, a scheme is presented which proposes divergent evolution of strains from a common ancestry. Furthermore, it was found that mutations were not restricted to the genes coding for the hemagglutinin and the neuraminidase, but were scattered throughout the genome, suggesting that selective antibody pressure is not solely responsible for the emergence of genetic variants. Our data also strengthen the hypothesis that the new H1N1 influenza virus strains are derived from strains circulating in 1950.

Antigens, Viral↗

Inference and prediction of courses of the diseases caused by pathologic viruses by estimating molecular evolution of within-host virus.

A new approach for inferring the evolutionary process of within-host virus is presented in this study. This approach includes a sequential-linking algorithm developed by us that can deal with the sequential viral samples that are obtained at different time points from the same host, and reconstruct a longitudinal phylogenetic tree in which the evolutionary relations between viral variants can be shown. A codon-based model, which uses a Markov process to describe substitutions between codons, is also employed in this approach to calculate synonymous and non-synonymous substitution rates and to distinguish positive selection and neutral evolution. The approach is applied to a data set of the V3 region of the HIV-1 envelope genes sequenced in different years after infection of a single patient. The results suggest that this approach may provide a more realistic description of viral evolution than the traditional evolution models because it accounts for both neutral and adaptive evolution. Most important of all, since this approach make it possible to follow up the evolutionary process of within-host virus by analyzing the sequential viral samples, it could be used in inference and prediction of the course of the diseases caused by pathologic viruses and evaluation of the treatment.

Algorithms↗

Molecular epidemiology of viral infections. How sequence information helps us understand the evolution and dissemination of viruses.

Viruses evolve much faster than cellular organisms. Together with recent advances in nucleic acid sequencing and biocomputing, this allows us to distinguish between related strains of viruses, and to deduce the relationships between viruses from different outbreaks or individual patients. Databases of nucleotide sequences contain a large number of viral sequences with which novel sequences from local outbreaks can be compared. In this way the dissemination of viruses can be followed both locally and globally. We here review the biological and technological background to the use of virus nucleic acid sequences in epidemiological studies, and provide examples of how this information can be used to monitor human viruses. Molecular studies are particularly valuable for understanding the dissemination and evolution of viruses. The knowledge obtained is useful in epidemiological reconstructions, in real-time surveillance, and may even enable us to make predictions about the future developments of viral diseases.

Animals↗

The core 2 beta-1,6-N-acetylglucosaminyltransferase-mucin encoded by bovine herpesvirus 4 was acquired from an ancestor of the African buffalo.

The Bo17 gene of bovine herpesvirus 4 (BoHV-4) is the only viral gene known to date that encodes a homologue of the cellular core 2 beta-1,6-N-acetylglucosaminyltransferase-mucin type (C2GnT-M). To investigate the origin and evolution of the Bo17 gene, we analyzed its distribution among BoHV-4 strains and determined the sequences of Bo17 from nine representative strains and of the C2GnT-M gene from six species of ruminants expected to encompass the group within which the gene acquisition occurred. Of 34 strains of BoHV-4, isolated from four different continents, all were found to contain the Bo17 gene. Phylogenetic analyses indicated that Bo17 was acquired from a recent ancestor of the African buffalo, implying that cattle subsequently acquired BoHV-4 by cross-species transmission. The rate of synonymous nucleotide substitution in Bo17 was estimated at 5 x 10(-8) to 6 x 10(-8) substitutions/site/year, consistent with previous estimates made under the assumption that herpesviruses have cospeciated with their hosts. The Bo17 gene acquisition was dated to around 1.5 million years ago. Bo17 sequences from BoHV-4 strains from African buffalo and from cattle formed two separate clades, estimated to have split about 700,000 years ago. Analysis of the ratio of nonsynonymous to synonymous nucleotide substitutions revealed a burst of amino acid replacements subsequent to the transfer of the cellular gene to the viral genome, followed by a return to a strong constraint on nonsynonymous changes during the divergence of contemporary BoHV-4 strains. The Bo17 gene represents the most recent of the known herpesvirus gene acquisitions and provides the best opportunity for learning more about this important process of viral evolution.

Amino Acid Sequence↗

Virus fitness: concept, quantification, and application to HIV population dynamics.

Viral fitness has been broadly studied during the past three decades, mainly to test evolutionary models and population theories difficult to analyze and interpret with more complex organisms. More recent studies, however, are focused in the role of fitness on viral transmission, pathogenesis, and drug resistance. Here, we used human immunodeficiency virus (HIV) as one of the most relevant models to evaluate the importance of viral quasispecies and fitness in HIV evolution, population dynamics, disease progression, and potential clinical implications.

Anti-HIV Agents↗