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PubMed1988

Structure, function, and intracellular processing of paramyxovirus membrane proteins.

Paramyxoviruses are a fascinating group of viruses with diverse hosts and disease manifestations. They are valuable systems for studying viral pathogenesis, molecular mechanisms of negative strand viral replication, and glycoprotein structure and function. In the past few years this group of viruses has received increased attention and as a result there is a wealth of new information. For example, most of the genes of many paramyxoviruses have been cloned and sequenced. The recent availability of sequence information from a number of paramyxoviruses now allows the direct comparison of the amino acid sequence and determinants of secondary structure of analogous genes across the family of viruses. Such comparisons are revealing for two reasons. First, results provide clues to the evolution of these viruses. Second, and more importantly, comparisons of analogous genes may point to sequences and structural determinants that are central to the function of the individual proteins. Below is a comparison of five of the paramyxovirus genes with a discussion of the implications of common structural determinants for function, intracellular processing, and evolutionary origin. The focus is on the paramyxovirus membrane proteins, although other proteins are discussed briefly.

Amino Acid Sequence↗
PubMed2003

The natural host range shift and subsequent evolution of canine parvovirus resulted from virus-specific binding to the canine transferrin receptor.

Canine parvovirus (CPV) is a host range variant of a feline virus that acquired the ability to infect dogs through changes in its capsid protein. Canine and feline viruses both use the feline transferrin receptor (TfR) to infect feline cells, and here we show that CPV infects canine cells through its ability to specifically bind the canine TfR. Receptor binding on host cells at 37 degrees C only partially correlated with the host ranges of the viruses, and an intermediate virus strain (CPV type 2) bound to higher levels on cells than did either the feline panleukopenia virus or a later strain of CPV. During the process of adaptation to dogs the later variant strain of CPV gained the ability to more efficiently use the canine TfR for infection and also showed reduced binding to feline and canine cells compared to CPV type 2. Differences on the top and the side of the threefold spike of the capsid surface controlled specific TfR binding and the efficiency of binding to feline and canine cells, and these differences also determined the cell infection properties of the viruses.

Amino Acid Sequence↗
PubMed1992

Convergent and divergent sequence evolution in the surface envelope glycoprotein of human immunodeficiency virus type 1 within a single infected patient.

In an investigation of the evolution of the third hypervariable loop of gp120 (V3), the principal neutralization determinant of human immunodeficiency virus type 1, we have analyzed 89 V3 sequences of plasma viral RNA purified from peripheral blood samples donated over 7 years by an infected hemophiliac. Considerable sequence diversity in the V3 region was found at all time points after seroconversion. Phylogenetic analysis revealed that an important diversification had occurred by 3 years postinfection and that, subsequently, most sequences could be allocated to either one of two major lineages that persisted throughout the remainder of the infection. Rapid changes in frequency of the most common sequences and the observation that the same hexapeptide motif (GPGSAV) at the crown of the V3 loop has evolved convergently provide strong evidence that selective processes determine the evolutionary fate of sequence variants in this region.

Amino Acid Sequence↗
PubMed1999

Independence of evolutionary and mutational rates after transmission of avian influenza viruses to swine.

In 1979, an H1N1 avian influenza virus crossed the species barrier, establishing a new lineage in European swine. Because there is no direct or serologic evidence of previous H1N1 strains in these pigs, these isolates provide a model for studying early evolution of influenza viruses. The evolutionary rates of both the coding and noncoding changes of the H1N1 swine strains are higher than those of human and classic swine influenza A viruses. In addition, early H1N1 swine isolates show a marked plaque heterogeneity that consistently appears after a few passages. The presence of a mutator mutation was postulated (C. Scholtissek, S. Ludwig, and W. M. Fitch, Arch. Virol. 131:237-250, 1993) to account for these observations and the successful establishment of an avian H1N1 strain in swine. To address this question, we calculated the mutation rates of A/Mallard/New York/6750/78 (H2N2) and A/Swine/Germany/2/81 (H1N1) by using the frequency of amantadine-resistant mutants. To account for the inherent variability of estimated mutation rates, we used a probabilistic model for the statistical analysis. The resulting estimated mutation rates of the two strains were not significantly different. Therefore, an increased mutation rate due to the presence of a mutator mutation is unlikely to have led to the successful introduction of avian H1N1 viruses in European swine.

Animals↗
PubMed2003

Evolution of coreceptor use and CD4-independence in envelope clones derived from SIVsm-infected macaques.

Coreceptor use of HIV can evolve during infection. We previously examined coreceptor use of related SIVsm inoculum viruses and sequential reisolates from cynomolgus macaques. These viruses exhibited broad coreceptor specificities and, generally, CCR5 use remained efficient and stable, while alternative coreceptor use decreased longitudinally. Here we demonstrate that individual envelopes (Envs) from inoculum and reisolate viruses fuse via a range of coreceptors, including CCR5, CCR8, CXCR6, GPR15, GPR1, and APJ. On the whole, coreceptor use of Envs from sequential reisolates recapitulated that of reisolate viruses, thus CCR5 use remained stable while alternative coreceptor use tended to decrease over time. Rhesus CCR5, GPR15, and CXCR6 supported fusion to a similar extent as their human counterparts. Additionally, a number of Envs mediated CD4-independent fusion via CCR5 and GPR15. Envs from different inoculum viruses exhibited distinct dependencies on CD4 for fusion via CCR5, ranging from strictly CD4-dependent to efficiently CD4-independent. Early reisolates from macaques infected with CD4-independent inoculums maintained or evolved Envs with a broad range of CD4-independence. CD4-independence became less variable/efficient in late reisolates from macaques that developed neutralizing antibodies. Infection with a CD4-dependent virus resulted in evolution of CD4-independent Envs in late reisolates. While CD4 independence can potentially broaden tropism in vivo, CD4-independent viruses are particularly sensitive to neutralizing antibodies. Therefore, interplay between receptor tropism and neutralization may shape viral evolution and SIV pathogenesis.

Animals↗
PubMed1994

Was exposure to directly antiviral cytokines during primary infection an important selective pressure in the evolution of unique immune evasion strategies by viruses?

Different virus families are characterized by various immune evasion strategies. These viruses have co-evolved with an increasingly sophisticated mammalian immune system which has continually placed pressure on their continued survival. This paper proposes that exposure to directly antiviral cytokines, namely TNF and members of the IFN family, during inflammatory and early immune responses, exerted particularly strong selective pressures on viruses, and has had a critical influence on the development of viral immune evasion strategies and pathogenesis. In the context of antiviral cytokine activity, this report concentrates on two DNA virus families with contrasting pathogenic and immune evasion strategies, namely poxviruses and HSV.

Animals↗
PubMed2006

Natural history of human respiratory syncytial virus inferred from phylogenetic analysis of the attachment (G) glycoprotein with a 60-nucleotide duplication.

A total of 47 clinical samples were identified during an active surveillance program of respiratory infections in Buenos Aires (BA) (1999 to 2004) that contained sequences of human respiratory syncytial virus (HRSV) with a 60-nucleotide duplication in the attachment (G) protein gene. This duplication was analogous to that previously described for other three viruses also isolated in Buenos Aires in 1999 (A. Trento et al., J. Gen. Virol. 84:3115-3120, 2003). Phylogenetic analysis indicated that BA sequences with that duplication shared a common ancestor (dated about 1998) with other HRSV G sequences reported worldwide after 1999. The duplicated nucleotide sequence was an exact copy of the preceding 60 nucleotides in early viruses, but both copies of the duplicated segment accumulated nucleotide substitutions in more recent viruses at a rate apparently higher than in other regions of the G protein gene. The evolution of the viruses with the duplicated G segment apparently followed the overall evolutionary pattern previously described for HRSV, and this genotype has replaced other prevailing antigenic group B genotypes in Buenos Aires and other places. Thus, the duplicated segment represents a natural tag that can be used to track the dissemination and evolution of HRSV in an unprecedented setting. We have taken advantage of this situation to reexamine the molecular epidemiology of HRSV and to explore the natural history of this important human pathogen.

Amino Acid Sequence↗
PubMed2006

Cryo-EM structure of a bacteriophage T4 gp24 bypass mutant: the evolution of pentameric vertex proteins in icosahedral viruses.

Many large viral capsids require special pentameric proteins at their fivefold vertices. Nevertheless, deletion of the special vertex protein gene product 24 (gp24) in bacteriophage T4 can be compensated by mutations in the homologous major capsid protein gp23. The structure of such a mutant virus, determined by cryo-electron microscopy to 26 angstroms, shows that the gp24 pentamers are replaced by mutant major capsid protein (gp23) pentamers at the vertices, thus re-creating a viral capsid prior to the evolution of specialized major capsid proteins and vertex proteins. The mutant gp23* pentamer is structurally similar to the wild-type gp24* pentamer but the insertion domain is slightly more distant from the gp23* pentamer center. There are additional SOC molecules around the gp23* pentamers in the mutant virus that were not present around the gp24* pentamers in the wild-type virus.

Biological Evolution↗
PubMed1995

Risks and benefits of interferon-alpha in the treatment of hepatitis.

The high worldwide prevalence of chronic viral hepatitis, as well as its progressive course, have led to the performance of multiple clinical studies. The natural history of the disease is different depending on the infecting virus; thus, the evolution to liver cirrhosis and/or hepatocellular carcinoma for the hepatitis B, C and delta (D) viruses in chronic hepatitis is 15, 20 and 75%, respectively. Different therapeutic agents have been used in attempts to modify the natural course of these diseases, interferon-alpha (IFN alpha) having proved to be the most effective. In 30 to 50% of patients, treatment with IFN alpha has achieved inhibition of viral replication, as well as normalisation of aminotransferase levels. Moreover, in a majority of patients, histological improvement is observed, principally in piece-meal necrosis and portal inflammation. The dosage currently recommended for treatment of chronic hepatitis B is 30 to 35MU weekly for a minimum of 4 months; when there is a co-existing delta virus infection, the total dosage employed should be greater. For hepatitis C, the minimum effective dosage is 9MU weekly, and a treatment duration of 12 months is recommended. The administration of IFN alpha produces a series of dose-dependent adverse effects, which are reversible on suspension of the medication. The most frequent of these adverse reactions is the 'flu-like' syndrome, which is self-limited and generally well tolerated. Secondary haematological alterations (leucopenia and thrombocytopenia) are the most frequent cause of reduction in dosage or suspension of treatment, although the latter is not normally necessary. The proportion of patients requiring dosage modification or suspension of treatment fluctuates between 5 and 15%. Taking the evolution of chronic hepatitis into account, there can be no doubt that all patients with this disease should be offered treatment. At present, the drug of choice is IFN alpha, as it slows disease progression and it is generally well tolerated.

Hepatitis↗
PubMed2002

Biological and serological variability, evolution and molecular epidemiology of Zucchini yellow mosaic virus (ZYMV, Potyvirus) with special reference to Caribbean islands.

Zucchini yellow mosaic virus (ZYMV, Potyvirus) emerged as an important pathogen of cucurbits within the last 20 years. Its origins and mechanisms for evolution and worldwide spread represent important questions to understand plant virus emergence. Sequence analysis on a 250 nucleotide fragment including the N-terminal part of the coat protein coding region, revealed one major group of strains, and some highly divergent isolates from distinct origins. Within the major group, three subsets of strains were defined without correlation with geographic origin, year of collection or biological properties. ZYMV was first observed in Martinique and Guadeloupe in 1992 and 1994, respectively. We studied the evolution of ZYMV variability on both islands in the few years following the putative virus introduction. In Martinique, molecular divergence remained low even after 6 years, suggesting a lack of new introductions. Interactions between strains resulted in a stability of the high biological variability, while the serological diversity decreased and molecular divergence remained low. In Guadeloupe, as in Martinique in 1993, serological variability was high shortly after virus introduction. While the first introduction in Guadeloupe was independent from Martinique, the 'Martinique' type was detected in 1998, suggesting further introductions, maybe through viruliferous aphids or imported plant material.

Amino Acid Sequence↗
PubMed1988

Seroepidemiology of human immunodeficiency viruses in Africa.

The first generation of serological tests for anti-HIV-1 gave so many false positives with African sera that it was wrongly postulated that the virus was endemic in Africa. As there is no simian or other virus sufficiently closely related to HIV-1 as to suggest a recent common ancestor, the evolution of HIV-1 is obscure and there is no current evidence to support the hypothesis of an African origin. However, the similarity of HIV-2 to SIV and its geographical distribution do suggest an evolution of this virus in west Africa. The earliest anti-HIV-1 positive serum was from a subject in Kinshasa in 1959. Seroprevalence rose in pregnant women in Kinshasa from 0.25% in 1970, to 3.0% in 1980 and 5.7% in 1986. When two sexually promiscuous groups are compared, seropositivity rose sharply in female prostitutes in Nairobi from 4% in 1981, to 59% in 1984 and 64% in 1986, a curve which is approximately parallel to, but three years later than that of homosexual males in San Francisco. In central and east Africa, HIV-1 is now epidemic from Congo to Kenya and from Uganda to Zimbabwe. In west Africa, both HIV-2 and HIV-1 are epidemic: seroprevalence of HIV-2 is highest in southern Senegal, Guinea-Bissau and Côte d'Ivoire: HIV-1 has the highest frequency in Côte d'Ivoire and Ghana. HIV-2 has not been reported, and HIV-1 is pre-epidemic in Africa north of the Sahara, Nigeria, Angola, Mozambique and southern Africa, being found at significant frequency only in female prostitutes, patients with STD, or, in Morocco and South Africa only, in male homosexuals. Seroprevalence is greatest in female prostitutes and patients with STD: infection is more frequent in urban than in rural populations, except in Uganda. The peak frequency is at 30-34 yr in males and 20-24 yr in females. Other groups at risk are infants born to infected mothers, and those requiring blood transfusions, especially pre-school children, patients with sickle-cell disease and pregnant women. The doubling time for seropositivity is about one year in the sexually active age range in some populations. Even at existing seroprevalence, decimation or worse of the most productive age groups is inevitable during the next few years in certain countries.(ABSTRACT TRUNCATED AT 400 WORDS)

AIDS Serodiagnosis↗
PubMed2005

New evolutionary frontiers from unusual virus genomes.

The sequences of two giant viral genomes, Mimivirus and a polydnavirus, have recently been published. Mimivirus has the largest known viral genome and encodes an unprecedented number of proteins, whereas the polydnavirus genome has an extremely low coding density and does not encode DNA-replication proteins. These and other unusual features challenge the way we view the evolution and definition of viruses.

Animals↗
PubMed1999

Variation of hepatitis C virus following serial transmission: multiple mechanisms of diversification of the hypervariable region and evidence for convergent genome evolution.

We have studied the evolution of hepatitis C virus (HCV) from a common source following serial transmission from contaminated batches of anti-D immunoglobulin. Six secondary recipients were each infected with virus from identifiable primary recipients of HCV-contaminated anti-D immunoglobulin. Phylogenetic analysis of virus E1/E2 gene sequences [including the hypervariable region (HVR)] and part of NS5B confirmed their common origin, but failed to reproduce the known epidemiological relationships between pairs of viruses, probably because of the frequent occurrence of convergent substitutions at both synonymous and nonsynonymous sites. There was no evidence that the rate at which the HCV genome evolves is affected by transmission events. Three different mechanisms appear to have been involved in generating variation of the hypervariable region; nucleotide substitution, insertion/deletion of nucleotide triplets at the E1/E2 boundary and insertion of a duplicated segment replacing almost the entire HVR. These observations have important implications for the phylogenetic analysis of HCV sequences from epidemiologically linked isolates.

Adolescent↗
PubMed1987

Genome similarities between plant and animal RNA viruses.

Gene sequence comparisons and protein comparisons provide more and more evidence that evolutionary links exist between plant and animal RNA viruses, irrespective of whether they have an isometric or rod-shaped particle, or of whether they have a divided or non-divided genome. Although a phylogeny based on these molecular data cannot yet be constructed the results obtained so far shed a new light on the origin and evolution of RNA viruses and are important in terms of their taxonomy.

Biological Evolution↗
PubMed2006

Prospects for universal influenza virus vaccine.

The current vaccination strategy against influenza A and B viruses is vulnerable to the unanticipated emergence of epidemic strains that are poorly matched by the vaccine. A vaccine that is less sensitive to the antigenic evolution of the virus would be a major improvement. The general feasibility of this goal is supported by studies in animal models that show that immunologic activities directed against relatively invariant viral determinants can reduce illness and death. The most promising approaches are based on antibodies specific for the relatively conserved ectodomain of matrix protein 2 and the intersubunit region of hemagglutinin. However, additional conserved determinants for protective antibodies are likely to exist, and their identification should be encouraged. Most importantly, infection and current vaccines do not appear to effectively induce these antibodies in humans. This finding provides a powerful rationale for testing the protective activity of these relatively conserved viral components in humans.

Antibodies, Viral↗