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PubMed2003

'Complementing' viral infection: mechanisms for evading innate immunity.

Through co-evolution with their hosts, viruses have developed a variety of immune escape and control mechanisms. In addition to strategies used to avoid the cellular and humoral immune responses, many viral families encode proteins capable of neutralizing the host's first line of defense, complement. The diversity of these complement avoidance mechanisms and proposed mechanisms by which viruses not only avoid, but also use the immune system to their advantage are discussed.

Animals↗

PubMed1980

[Clinical aspects of viral respiratory infections].

The Authors deal with some clinical aspect of the commonest types of respiratory tract viral infections. After a description of the characteristics of the most important diseases (common cold, ARD, influenza, viral pneumonia) they deal with some particular problem difficult in resolution, both from a pathogenetic and clinical viewpoint and quite constant bacterial over infection, the cardiac complications, th possible evolution to fibrosis and the relationship between viral infections and asthma. The nowadays problem of immunological and chemotherapeutic prevention of viral infections, particularly of type A influenza, is also discussed.

Adenoviridae Infections↗

PubMed1987

[Acquired immunologic deficiency syndrome (AIDS). I. Biologic principles].

AIDS is a transmissible immunodeficiency syndrome which has first been observed less than a decade ago and since that time has spread in an epidemic manner. Usually it manifests itself by opportunistic infections and/or neoplasias. After courses of a few years, approximately 100% of cases have a lethal outcome. Sometimes, neuropsychiatric disturbances are the presenting symptoms and signs of AIDS. One of the first important observations was, that certain behavioural patterns such as homosexuality and intravenous drug abuse were apparently associated with a high risk for acquiring AIDS. The occurrence of AIDS in a number of haemophiliacs and recipients of blood transfusions suggested an important role of the haematogenous route of transmission. Not more than two years after the first clinical reports on AIDS a retrovirus was identified as the etiological agent. On the basis of different criteria this retrovirus can be classified as a slow virus. Subsequently, virological tests were developed which allowed an early diagnosis of this viral infection, even prior to the evolution of clinical symptoms. Immunological features of this new syndrome include disturbances of cellular as well as humoral immune functions. As we have no effective chemotherapy for AIDS and the successful development of a vaccine is delayed by a number of virological problems, it is of special importance to prevent transmission of the disease.

Acquired Immunodeficiency Syndrome↗

PubMed2006

Evolutionary genomics of nucleo-cytoplasmic large DNA viruses.

A previous comparative-genomic study of large nuclear and cytoplasmic DNA viruses (NCLDVs) of eukaryotes revealed the monophyletic origin of four viral families: poxviruses, asfarviruses, iridoviruses, and phycodnaviruses [Iyer, L.M., Aravind, L., Koonin, E.V., 2001. Common origin of four diverse families of large eukaryotic DNA viruses. J. Virol. 75 (23), 11720-11734]. Here we update this analysis by including the recently sequenced giant genome of the mimiviruses and several additional genomes of iridoviruses, phycodnaviruses, and poxviruses. The parsimonious reconstruction of the gene complement of the ancestral NCLDV shows that it was a complex virus with at least 41 genes that encoded the replication machinery, up to four RNA polymerase subunits, at least three transcription factors, capping and polyadenylation enzymes, the DNA packaging apparatus, and structural components of an icosahedral capsid and the viral membrane. The phylogeny of the NCLDVs is reconstructed by cladistic analysis of the viral gene complements, and it is shown that the two principal lineages of NCLDVs are comprised of poxviruses grouped with asfarviruses and iridoviruses grouped with phycodnaviruses-mimiviruses. The phycodna-mimivirus grouping was strongly supported by several derived shared characters, which seemed to rule out the previously suggested basal position of the mimivirus [Raoult, D., Audic, S., Robert, C., Abergel, C., Renesto, P., Ogata, H., La Scola, B., Suzan, M., Claverie, J.M. 2004. The 1.2-megabase genome sequence of Mimivirus. Science 306 (5700), 1344-1350]. These results indicate that the divergence of the major NCLDV families occurred at an early stage of evolution, prior to the divergence of the major eukaryotic lineages. It is shown that subsequent evolution of the NCLDV genomes involved lineage-specific expansion of paralogous gene families and acquisition of numerous genes via horizontal gene transfer from the eukaryotic hosts, other viruses, and bacteria (primarily, endosymbionts and parasites). Amongst the expansions, there are multiple families of predicted virus-specific signaling and regulatory domains. Most NCLDVs have also acquired large arrays of genes related to ubiquitin signaling, and the animal viruses in particular have independently evolved several defenses against apoptosis and immune response, including growth factors and potential inhibitors of cytokine signaling. The mimivirus displays an enormous array of genes of bacterial provenance, including a representative of a new class of predicted papain-like peptidases. It is further demonstrated that a significant number of genes found in NCLDVs also have homologs in bacteriophages, although a vertical relationship between the NCLDVs and a particular bacteriophage group could not be established. On the basis of these observations, two alternative scenarios for the origin of the NCLDVs and other groups of large DNA viruses of eukaryotes are considered. One of these scenarios posits an early assembly of an already large DNA virus precursor from which various large DNA viruses diverged through an ongoing process of displacement of the original genes by xenologous or non-orthologous genes from various sources. The second scenario posits convergent emergence, on multiple occasions, of large DNA viruses from small plasmid-like precursors through independent accretion of similar sets of genes due to strong selective pressures imposed by their life cycles and hosts.

Amino Acid Sequence↗

PubMed2002

Molecular indetermination in the transition to error catastrophe: systematic elimination of lymphocytic choriomeningitis virus through mutagenesis does not correlate linearly with large increases in mutant spectrum complexity.

Studies with several RNA viruses have shown that enhanced mutagenesis resulted in decreases of infectivity or virus extinction, as predicted from virus entry into error catastrophe. Here we report that lymphocytic choriomeningitis virus, the prototype arenavirus, is extremely susceptible to extinction mutagenesis by the base analog 5-fluorouracil. Virus elimination was preceded by increases in complexity of the mutant spectra of treated populations. However, careful molecular comparison of the mutant spectra of several genomic segments suggests that the largest increases in mutation frequency do not predict virus extinction. Highly mutated viral genomes have escaped detection presumably because lymphocytic choriomeningitis virus replicates at or near the error threshold, and genomes in the transition toward error catastrophe may have an extremely short half-life and escape detection with state-of-the-art cloning and sequencing technologies.

Animals↗

PubMed2005

Marine phage genomics: what have we learned?

Marine phages are the most abundant and diverse form of life on the planet, and their genomes have been described as the largest untapped reservoir of genomic information. To date, however, the complete genome sequences of only 17 marine phage are known. Nevertheless, these genomes have revealed some interesting features, including the presence of photosynthetic genes in cyanophage and common patterns of genomic organization. Intriguing findings are also being made from studies of the uncultivated marine viral community genome ('metavirome'). The greatest challenge in interpreting the biology of these phages, and for making comparisons with their terrestrial counterparts, is the high proportion of unidentifiable open reading frames (approximately 60%). Future studies are likely to focus on sequencing more marine phage genomes from disparate hosts and diverse environments and on further basic studies of the biology of existing marine phages.

Bacteriophages↗

PubMed1999

Comparative sequence analysis of the DNA packaging, head, and tail morphogenesis modules in the temperate cos-site Streptococcus thermophilus bacteriophage Sfi21.

The temperate Streptococcus thermophilus bacteriophage Sfi21 possesses 15-nucleotide-long cohesive ends with a 3' overhang that reconstitutes a cos-site with twofold hyphenated rotational symmetry. Over the DNA packaging, head and tail morphogenesis modules, the Sfi21 sequence predicts a gene map that is strikingly similar to that of lambdoid coliphages in the absence of any sequence similarity. A nearly one to one gene correlation was found with the phage lambda genes Nu1 to H, except for gene B-to-E complex, where the Sfi21 map resembled that of coliphage HK97. The similarity between Sfi21 and HK97 was striking: both major head proteins showed an N-terminal coiled-coil structure, the mature major head proteins started at amino acid positions 105 and 104, respectively, and both major head genes were preceded by genes encoding a possible protease and portal protein. The purported Sfi21 protease is the first viral member of the ClpP protease family. The prediction of Sfi21 gene functions by reference to the gene map of intensively investigated coliphages was experimentally confirmed for the major head and tail gene. Phage Sfi21 shows nucleotide sequence similarity with Lactococcus phage BK5-T and a lactococcal prophage and amino acid sequence similarity with the Lactobacillus phage A2 and the Staphylococcus phage PVL. PVL is a missing link that connects the portal proteins from Sfi21 and HK97 with respect to sequence similarity. These observations and database searches, which demonstrate sequence similarity between proteins of phage from gram-positive bacteria, proteobacteria, and Archaea, constrain models of phage evolution.

Amino Acid Sequence↗

PubMedDate not supplied

[Intrathecal humoral immune response in pediatric patients with meningoencephalitis due to Coxsackie B5].

INTRODUCTION: Childhood is sensibly affected by viral meningoencephalitis outbreaks. OBJECTIVE: To study the intrathecal humoral immune response in a group of children suffering from Coxsackie B5 meningoencephalitis outbreak. Patients and methods. Forty eight sick children were studied. Serum and cerebrospinal IgA, IgM, IgG and albumin were quantified by radial immunodiffusion. It had been evaluated by reibergrams. RESULTS: Seventeen children has blood-cerebrospinal fluid barrier dysfunction. Four different patterns of intrathecal immune humoral response were observed mainly IgG and three major immunoglobulins class. Mean cell counts was 624 +/- 517 x 10(6) cells/l with a lymphocyte predominance. CONCLUSION: An intrathecal humoral response were reported as an early patterns like in delayed non-diagnostic puncture and in evolutive puncture in adults patterns with viral meningoencephalitis.

Antibodies, Viral↗

PubMed2006

Evolutionary genomics of archaeal viruses: unique viral genomes in the third domain of life.

In terms of virion morphology, the known viruses of archaea fall into two distinct classes: viruses of mesophilic and moderately thermophilic Eueryarchaeota closely resemble head-and-tail bacteriophages whereas viruses of hyperthermophilic Crenarchaeota show a variety of unique morphotypes. In accord with this distinction, the sequenced genomes of euryarchaeal viruses encode many proteins homologous to bacteriophage capsid proteins. In contrast, initial analysis of the crenarchaeal viral genomes revealed no relationships with bacteriophages and, generally, very few proteins with detectable homologs. Here we describe a re-analysis of the proteins encoded by archaeal viruses, with an emphasis on comparative genomics of the unique viruses of Crenarchaeota. Detailed examination of conserved domains and motifs uncovered a significant number of previously unnoticed homologous relationships among the proteins of crenarchaeal viruses and between viral proteins and those from cellular life forms and allowed functional predictions for some of these conserved genes. A small pool of genes is shared by overlapping subsets of crenarchaeal viruses, in a general analogy with the metagenome structure of bacteriophages. The proteins encoded by the genes belonging to this pool include predicted transcription regulators, ATPases implicated in viral DNA replication and packaging, enzymes of DNA precursor metabolism, RNA modification enzymes, and glycosylases. In addition, each of the crenarchaeal viruses encodes several proteins with prokaryotic but not viral homologs, some of which, predictably, seem to have been scavenged from the crenarchaeal hosts, but others might have been acquired from bacteria. We conclude that crenarchaeal viruses are, in general, evolutionarily unrelated to other known viruses and, probably, evolved via independent accretion of genes derived from the hosts and, through more complex routes of horizontal gene transfer, from other prokaryotes.

Amino Acid Sequence↗

PubMed1997

Coat protein gene and 3'-noncoding region of a new Korean isolate of cymbidium mosaic virus.

A new Korean isolate of cymbidium mosaic virus (denoted as CymMV-K2), a member of potexviruses, was identified and isolated from a Korean cultivar of Cymbidium species When the nucleotide sequence of the 3'-terminal region of the viral RNA was compared with those of the corresponding regions of two Singaporean isolates (denoted as CymMV-S1 and CymMV-S2) and a Korean isolate (denoted as CymMV-K1), the nucleotide sequence of the coat protein gene of CymMV-K2 was highly homologous to other cymbidium mozaic viruses (92.9%-96.7% homology). The coat protein of CymMV-K2 and CymMV-S2 consists of 223 amino acids, while the coat protein of CymMV-K1 and CymMV-S1 consists of 220 amino acids. This difference was caused by deletions of 5 nucleotides in the coat protein open reading frame (ORF) of CymMV-S1 and CymMV-K1, when compared with CymMV-K2 and CymMV-S2. These deletions result in changes of the deduced amino acid sequence and the length of the coat protein. The 3'-noncoding region of the CymMV-K2, which contains sequences involved in the replication and polyadenylation of viral RNA, was compared with those of other cymbidium mosaic viruses. No canonical polyadenylation signal was found in the 3'-noncoding region of CymMV-K2, whereas in other CymMVs AAUAAA boxes, are present at the end of RNA with their AAA portions as the first A residue of the poly(A) tail.

Amino Acid Sequence↗

PubMed2004

Technical knockout: understanding poxvirus pathogenesis by selectively deleting viral immunomodulatory genes.

The study of viral pathogens with genomes as large and complex as poxviruses represents a constant experimental challenge. Advances in recombinant DNA technologies have provided sophisticated methods to produce mutants defective in one or more viral genes, termed knockout (KO) viruses, thereby facilitating research into the impact of specific gene products on viral pathogenesis. Such strategies have rapidly advanced the systematic mining of many poxvirus genomes and enabled researchers to identify and characterize poxvirus genes whose functions represent the culmination of host and pathogen coevolution. Of particular interest are the multiple classes of virus-encoded immunomodulatory proteins that have evolved specifically to allow poxviruses to evade, obstruct or subvert critical elements within the host innate and acquired immune responses. Functional characterization of these viral genes by generating KO viruses and investigating the phenotypic changes that result is an important tool for understanding the molecular mechanisms underlying poxvirus replication and pathogenesis. Moreover, the insights gained have led to new developments in basic and clinical virology, provided a basis for the design of new vaccines and antivirals, and increased the potential application of poxviruses as investigative tools and sources of biotherapeutics for the treatment of human diseases.

Adjuvants, Immunologic↗

PubMed2006

Evolution of the susceptibility to antiviral drugs of A/H3N2 influenza viruses isolated in France from 2002 to 2005.

In 2002, prior to the generalization of zanamivir and oseltamivir utilization in France, we had decided to test a large panel of influenza strains to establish the baseline sensitivity of these viruses to anti-neuraminidase drugs. Since 2002, routine monitoring of resistance relies mainly on the results of neuraminidase enzyme assay. The profile of sensitivity of A/H3N2 viruses has not changed during these three influenza seasons. Neuraminidase N2 was shown to be more sensitive to oseltamivir carboxylate than to zanamivir. Amongst 788 viruses tested, only 10 were found with outliers IC(50) values (seven in 2003, one in 2004, and two in 2005). After the sequencing of the neuraminidase segment of these viruses, seven mutations on the stalk or the head of the glycoprotein (A18S, L23F, C42R, R143V, E199K, S332K, R431N) were detected. Moreover during seasons 2003-2005, 12 additional viruses were characterized by a complete lack of neuraminidase activity. In these viruses, viral resistance to NA inhibitors can be related with the presence of a defective neuraminidase RNA segment as evaluated by a plaque reduction assay, these viruses having a reduced dependence on its neuraminidase activity.

Antiviral Agents↗

PubMedDate not supplied

Polymorphism in HIV-1 non-subtype B protease and reverse transcriptase and its potential impact on drug susceptibility and drug resistance evolution.

HIV-1 non-subtype B viruses are predominant worldwide. At least 9 different HIV-1 group M subtypes and 14 circulating recombinant forms differ from one another by 10-15% in their pol gene, which includes the coding regions for the viral protease and reverse transcriptase (RT), the current targets of antiretroviral drugs. Inter-subtype genotypic diversity includes polymorphism at amino acid residues known to be related to drug resistance in HIV-1 subtype B. Whether polymorphism alters protease and RT function, drug susceptibility, or clinical response to treatment, is unclear. Worldwide dissemination of non-subtype B viruses and increasing availability of antiretroviral drugs in the developing world will expand drug use and the likelihood of drug resistance in non-subtype B viruses. In this review we define and characterize inter-subtype RT and protease polymorphism, and examine the evidence for genotypic and phenotypic differences between HIV-1 subtypes as well as the potential for different clinical responses and evolution of drug resistance among non-B infected individuals.

Anti-HIV Agents↗

PubMed1981

The p21 src genes of Harvey and Kirsten sarcoma viruses originate from divergent members of a family of normal vertebrate genes.

The Harvey and Kirsten strains of murine sarcoma virus encode enzymatically and serologically related p21 src proteins which are required for virally mediated cellular transformation. The genes in each virus encoding p21 show such extensive divergence from each other that cloned probes from these genes detect distinct sets of cellular genes in the DNA from several vertebrate species. These data suggest that cellular p21 sarc genes constitute a divergent family of vertebrate genes that can regulate the growth of cells.

Animals↗

PubMed2001

Common origin of four diverse families of large eukaryotic DNA viruses.

Comparative analysis of the protein sequences encoded in the genomes of three families of large DNA viruses that replicate, completely or partly, in the cytoplasm of eukaryotic cells (poxviruses, asfarviruses, and iridoviruses) and phycodnaviruses that replicate in the nucleus reveals 9 genes that are shared by all of these viruses and 22 more genes that are present in at least three of the four compared viral families. Although orthologous proteins from different viral families typically show weak sequence similarity, because of which some of them have not been identified previously, at least five of the conserved genes appear to be synapomorphies (shared derived characters) that unite these four viral families, to the exclusion of all other known viruses and cellular life forms. Cladistic analysis with the genes shared by at least two viral families as evolutionary characters supports the monophyly of poxviruses, asfarviruses, iridoviruses, and phycodnaviruses. The results of genome comparison allow a tentative reconstruction of the ancestral viral genome and suggest that the common ancestor of all of these viral families was a nucleocytoplasmic virus with an icosahedral capsid, which encoded complex systems for DNA replication and transcription, a redox protein involved in disulfide bond formation in virion membrane proteins, and probably inhibitors of apoptosis. The conservation of the disulfide-oxidoreductase, a major capsid protein, and two virion membrane proteins indicates that the odd-shaped virions of poxviruses have evolved from the more common icosahedral virion seen in asfarviruses, iridoviruses, and phycodnaviruses.

Amino Acid Sequence↗

PubMed2004

Limited T cell receptor diversity of HCV-specific T cell responses is associated with CTL escape.

Escape mutations are believed to be important contributors to immune evasion by rapidly evolving viruses such as hepatitis C virus (HCV). We show that the majority of HCV-specific cytotoxic T lymphocyte (CTL) responses directed against viral epitopes that escaped immune recognition in HCV-infected chimpanzees displayed a reduced CDR3 amino acid diversity when compared with responses in which no CTL epitope variation was detected during chronic infection or with those associated with protective immunity. Decreased T cell receptor (TCR) CDR3 amino acid diversity in chronic infection could be detected long before the appearance of viral escape mutations in the plasma. In both chronic and resolved infection, identical T cell receptor clonotypes were present in liver and peripheral blood. These findings provide a deeper understanding of the evolution of CTL epitope variations in chronic viral infections and highlight the importance of the generation and maintenance of a diverse TCR repertoire directed against individual epitopes.

Amino Acid Sequence↗

PubMed2004

Persistence of low levels of simian immunodeficiency virus in macaques that were transiently viremic by conventional testing.

Transient SIV viremia after experimental SIV challenge has been documented. Whether SIV persists in these transiently viremic macaques remains unclear. In the present study, we applied a sensitive PCR and found persistent low levels of SIVmne infection (LLSI) (range: 0.1-5.3 SIV DNA copies/10(6) PBMC) in seven macaques that were transiently positive by conventional assays, which was 10(2)- to 10(6)-fold less than those of SIVmne infected monkeys with typical disease progression. SIV envelope V1 sequences remained homogeneous in these macaques for the 6-year study period, with a mean evolution rate of 0.005% per site per year, which was not different from zero (P = 0.612) and significantly lower than that (0.56-1.18%) in macaques with progressive infection of SIVmne. LLSI macaques have remained free from SIV-associated illness, and are still alive 10 years after virus inoculation. Understanding the mechanisms underlying this outcome may provide valuable insight into therapy and vaccine development.

Amino Acid Sequence↗

PubMed2006

Tracing the origin of Brazilian HTLV-1 as determined by analysis of host and viral genes.

We compared the genetic diversity of the Brazilian human T-cell lymphotropic virus type 1 isolates with those found in KwaZulu-Natal (KZN), South Africa, and with the genetic background of the hosts. The seroprevalence rate in KZN was 1.7%. All sequences belonged to the A subgroup. The presence of South African sequences in two different clusters from Brazil, and the finding of the beta-globin haplotype in infected hosts are consistent with the transmission of this virus from southern Africa to Brazil.

Brazil↗