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T G Fanning

Publications and source records attributed to T G Fanning.

At least 19 recordsLinked to original sources
PubMed2003

Relationship of pre-1918 avian influenza HA and NP sequences to subsequent avian influenza strains.

Wild waterfowl that were captured between 1915 and 1919 and preserved in 70% ethyl alcohol were tested for influenza A virus RNA. Most of the HA1 domain of the hemagglutinin (HA) gene segment was sequenced from one bird, captured in 1917, that was infected with a virus of the same HA subtype as the 1918 human pandemic virus. The 1917 HA sequence is closely related to modern avian HA sequences, suggesting little drift in avian sequences in 80 years and that the 1918 pandemic virus probably did not acquire its hemagglutinin directly from a bird. A 151-bp fragment of the nucleoprotein gene segment was sequenced from two pre-1918 birds and compared to avian and mammalian influenza strains. The 1917 avian NP sequences are also closely related to modern avian sequences and distinct from the mammalian clade in which the 1918 NP sequence is found.

Amino Acid Sequence↗
PubMed2001

Integrating historical, clinical and molecular genetic data in order to explain the origin and virulence of the 1918 Spanish influenza virus.

The Spanish influenza pandemic of 1918-1919 caused acute illness in 25-30% of the world's population and resulted in the death of 40 million people. The complete genomic sequence of the 1918 influenza virus will be deduced using fixed and frozen tissues of 1918 influenza victims. Sequence and phylogenetic analyses of the complete 1918 haemagglutinin (HA) and neuraminidase (NA) genes show them to be the most avian-like of mammalian sequences and support the hypothesis that the pandemic virus contained surface protein-encoding genes derived from an avian influenza strain and that the 1918 virus is very similar to the common ancestor of human and classical swine H1N1 influenza strains. Neither the 1918 HA genes nor the NA genes possessed mutations that are known to increase tissue tropicity, which accounts for the virulence of other influenza strains such as A/WSN/33 or fowl plague viruses. The complete sequence of the nonstructural (NS) gene segment of the 1918 virus was deduced and tested for the hypothesis that the enhanced virulence in 1918 could have been due to type I interferon inhibition by the NS1 protein. The results from these experiments were inconclusive. Sequence analysis of the 1918 pandemic influenza virus is allowing us to test hypotheses as to the origin and virulence of this strain. This information should help to elucidate how pandemic influenza strains emerge and what genetic features contribute to their virulence.

Animals↗
PubMed2001

Sequence of the 1918 pandemic influenza virus nonstructural gene (NS) segment and characterization of recombinant viruses bearing the 1918 NS genes.

The influenza A virus pandemic of 1918-1919 resulted in an estimated 20-40 million deaths worldwide. The hemagglutinin and neuraminidase sequences of the 1918 virus were previously determined. We here report the sequence of the A/Brevig Mission/1/18 (H1N1) virus nonstructural (NS) segment encoding two proteins, NS1 and nuclear export protein. Phylogenetically, these genes appear to be close to the common ancestor of subsequent human and classical swine strain NS genes. Recently, the influenza A virus NS1 protein was shown to be a type I IFN antagonist that plays an important role in viral pathogenesis. By using the recently developed technique of generating influenza A viruses entirely from cloned cDNAs, the hypothesis that the 1918 virus NS1 gene played a role in virulence was tested in a mouse model. In a BSL3+ laboratory, viruses were generated that possessed either the 1918 NS1 gene alone or the entire 1918 NS segment in a background of influenza A/WSN/33 (H1N1), a mouse-adapted virus derived from a human influenza strain first isolated in 1933. These 1918 NS viruses replicated well in tissue culture but were attenuated in mice as compared with the isogenic control viruses. This attenuation in mice may be related to the human origin of the 1918 NS1 gene. These results suggest that interaction of the NS1 protein with host-cell factors plays a significant role in viral pathogenesis.

Amino Acid Sequence↗
PubMed2001

The 1918 Spanish influenza: integrating history and biology.

In 1918 an influenza pandemic killed 40 million people. It is now possible to study the genetic features of the 1918 virus. Such analyses will try to answer questions about the origin and the unusual virulence of this pandemic virus.

Disease Outbreaks↗
PubMed2000

Influenza A virus neuraminidase: regions of the protein potentially involved in virus-host interactions.

Phylogenetically informative amino acid positions (PIPs) were identified in influenza A neuraminidases of subtypes N1 and N2. Neuraminidase evolves in a lineage-specific way as the virus adapts to a new host or changes to evade the host's immune system. Thus, many PIPs undoubtedly identify positions involved in virus-host interactions. Phylogenetically important regions (PIRs) are defined as several PIPs near one another. There are 15 PIRs on N1 and 12 on N2, seven of which are shared between the two subtypes. Many PIRs are coincident with antigenic or glycosylation sites. Other PIRs may represent additional antigenic sites or may be involved in other aspects of virus-host biology.

Amino Acids↗
PubMed2000

Characterization of the 1918 "Spanish" influenza virus neuraminidase gene.

The "Spanish" influenza pandemic of 1918 was characterized by exceptionally high mortality, especially among young adults. The surface proteins of influenza viruses, hemagglutinin and neuraminidase, play important roles in virulence, host specificity, and the human immune response. The complete coding sequence of hemagglutinin was reported last year. This laboratory has now determined the complete coding sequence of the neuraminidase gene of the 1918 virus. Influenza RNA fragments were isolated from lung tissue of three victims of the 1918 flu; complete sequence was generated from A/Brevig Mission/1/18, with confirmatory sequencing carried out on A/South Carolina/1/18 and A/New York/1/18. The 1918 neuraminidase gene sequence was compared with other N1 subtype neuraminidase genes, including 9 N1 strains newly sequenced for this study. The 1918 neuraminidase shares many sequence and structural characteristics with avian strains, including the conserved active site, wild-type stalk length, glycosylation sites, and antigenic sites. Phylogenetically, the 1918 neuraminidase gene appears to be intermediate between mammals and birds, suggesting that it was introduced into mammals just before the 1918 pandemic.

Adult↗
PubMed1999

Phylogenetically important regions of the influenza A H1 hemagglutinin protein.

A parsimony approach was used to construct phylogenetic trees of the H1, H2 and H3 influenza hemagglutinin subtypes. The parsimony trees were then compared with randomly generated trees to identify regions of the proteins containing the most phylogenetic information, i.e. those regions making the parsimony trees shorter. We reasoned that any areas of the hemagglutinin protein that were phylogenetically 'information-rich' would be good candidates for sites involved in virus-host interactions and their identification might lead to a better understanding of the protein. Molecular modelling, based upon the crystal structure of the H3 hemagglutinin, demonstrated that most phylogenetically important regions of the H1 subtype were on the surface of the hemagglutinin trimer, primarily in the globular region. Many corresponded to known antigenic or receptor binding sites, while others appear to be novel and specific for H1.

Hemagglutinin Glycoproteins, Influenza Virus↗
PubMed1999

Characterization of Escherichia coli 50S ribosomal protein L31.

The published C-terminal sequence of Escherichia coli 50S ribosomal protein L31, ellipsisRFNK (Brosius, J. (1978) Biochemistry 17, 501-508), differs from that predicted by the gene sequence, ellipsisRFNKRFNIPGSK (GenBank accession no. X78541). This discrepancy might be due to post-translational processing of the protein. To examine this possibility, we have isolated L31 from E. coli strain MRE600 and sequenced the C-terminal tryptic peptide. We find the sequence to be FBIPGSK. Size comparisons of L31 from several E. coli strains demonstrate that all are identical in size to the protein isolated from MRE600 and larger than the previously described protein, indicating that ellipsisRFNKRFNIPGSK represents the true C-terminus of L31. In addition, we show that the failure to identify L31 in many ribosome preparations is probably due to the protein's loose association with the ribosome and its ability to form various intramolecular disulfide bonds, leading to L31 forms with distinct mobilities in gels.

Amino Acid Sequence↗
PubMed1999

Origin and evolution of the 1918 "Spanish" influenza virus hemagglutinin gene.

The "Spanish" influenza pandemic killed over 20 million people in 1918 and 1919, making it the worst infectious pandemic in history. Here, we report the complete sequence of the hemagglutinin (HA) gene of the 1918 virus. Influenza RNA for the analysis was isolated from a formalin-fixed, paraffin-embedded lung tissue sample prepared during the autopsy of a victim of the influenza pandemic in 1918. Influenza RNA was also isolated from lung tissue samples from two additional victims of the lethal 1918 influenza: one formalin-fixed, paraffin-embedded sample and one frozen sample obtained by in situ biopsy of the lung of a victim buried in permafrost since 1918. The complete coding sequence of the A/South Carolina/1/18 HA gene was obtained. The HA1 domain sequence was confirmed by using the two additional isolates (A/New York/1/18 and A/Brevig Mission/1/18). The sequences show little variation. Phylogenetic analyses suggest that the 1918 virus HA gene, although more closely related to avian strains than any other mammalian sequence, is mammalian and may have been adapting in humans before 1918.

Adult↗
PubMed1997

Initial genetic characterization of the 1918 "Spanish" influenza virus.

The "Spanish" influenza pandemic killed at least 20 million people in 1918-1919, making it the worst infectious pandemic in history. Understanding the origins of the 1918 virus and the basis for its exceptional virulence may aid in the prediction of future influenza pandemics. RNA from a victim of the 1918 pandemic was isolated from a formalin-fixed, paraffin-embedded, lung tissue sample. Nine fragments of viral RNA were sequenced from the coding regions of hemagglutinin, neuraminidase, nucleoprotein, matrix protein 1, and matrix protein 2. The sequences are consistent with a novel H1N1 influenza A virus that belongs to the subgroup of strains that infect humans and swine, not the avian subgroup.

Algorithms↗
PubMed1996

Comparative karyology and evolution of the Amazonian Callithrix (Platyrrhini, Primates).

Chromosomal studies in three species of Amazonian Callithrix (2n=44) and data in the literature show that this group is karyomonotypic. Moreover, it is characterized by the presence of abundant heterochromatic regions, unlike the situation in congeneric forms of Callithrix of the Atlantic coast with 2n=46, and by the presence of a highly repetitive, exclusive DNA component, with a basic repeat motif of 1528bp. Karyotypic comparisons with other Callitrichids and an outgroup species showed that Callitrichids are karyologically conserved and explained several rearrangements that had presumably occurred during their phyletic radiation. Analyses of karyologic data enabled the construction of two alternative phylogenetic topologies. The lack of derived homoeologies, common to all members of the genus Callithrix grouped at present, and the fact that Amazonian species were more similar to Cebuella pygmaea (2n=44) than to their congeneric forms with 2n=46 suggested that species at present included in the Amazonian Callithrix should be grouped with C. pygmaea.

Animals↗
PubMed1996

Comparative expression of the LINE-1 p40 protein in human breast carcinomas and normal breast tissues.

Human LINE-1 (L1Hs) retrotransposons can act as insertional mutagens and are expressed in a variety of tumors, including breast cancer. The purpose of the present study was to examine expression of the p40 protein encoded by the first open reading frame of a L1Hs element in normal human breast tissue of patients without malignant breast disease and in nontumor breast tissue adjacent to cancer and to compare it to expression in breast carcinomas. An antiserum specific for the L1Hs p40 protein was used to analyze its expression in 5 reduction mammoplasties, 16 primary breast cancers, 1 lymph node metastasis and 13 non-malignant breast tissues adjacent to matched primaries by western blotting and/or immunocytochemistry. The immunoreactive band observed on westerns consistently had a M(r) of approximately 46 kDa. Westerns detected some p40 protein expression in all malignant and nonmalignant tissues examined, although 4 of 5 reduction mammoplasties had very low or trace levels as compared with tumors. Nonmalignant breast tissues adjacent to cancers showed significant western band reactivity, and all 15 tumors were positive. Immunocytochemistry revealed staining specificity of the antibody for epithelial cells. Of 12 invasive carcinomas examined, 100% were positive for the p40 protein, whereas one reduction with benign proliferative disease was very weakly reactive, two histologically normal reductions were negative, and 4 of 6 nonmalignant tissues adjacent to cancers were negative. Our data indicated that expression of the L1Hs p40 protein was often elevated in tumor cells of human breast cancers compared to epithelium of normal mammary gland.

Adult↗
PubMed1994

Expression of LINE-1 retrotransposons in human breast cancer.

BACKGROUND: Several diseases have been linked to the insertion of human LINE-1 retrotransposons (L1Hs) into structural genes. Recently, the element has been shown to be expressed in a variety of adult and pediatric germ cell cancers, leading to speculation that L1Hs-induced insertion mutations may play a role in the etiology of some neoplasias. METHODS: An L1Hs-encoded protein (p40) was assayed in breast cancer cell lines by Western blotting and in solid tumors by immunohistochemical staining and Western blotting. RESULTS: L1Hs retrotransposons are expressed in a significant number of human breast cancers: expression was detected in 7 of 8 malignant cell lines and in 9 of 12 primary infiltrating ductal carcinomas. No expression was detected in two nonmalignant breast epithelial cell lines, five malignant B- or T-cell lines, tissue from a normal breast, a primary breast sarcoma, or a primary medullary carcinoma of the breast. CONCLUSIONS: These results raise the possibility that L1Hs expression may contribute to the origin or progression of some breast cancers.

Breast↗
PubMed1994

Phylogeny of the steroid receptor superfamily.

The phylogenetic relationships of 56 nuclear hormone receptors from both invertebrates and vertebrates were determined by the parsimony method (PAUP). The consensus tree suggests that the ancestral gene diverged into five major subfamilies, each of which evolved into at least one cluster of related molecules. These subfamilies are represented by: (1) thyroid hormone receptors (TR); (ii) steroid receptors (SR); (iii) retinoic acid receptors (RAR), retinoid X receptors (RXR), and the chicken ovalbumin upstream promoter transcription factor 1 (COUP) group; (ix) peroxisome proliferator-activated receptors (PPAR); and (v) vitamin D receptor (VDR) and knirps (kni) group. Although the neighbor-joining (N-J) method clustered the receptors into a greater number of subfamilies, it was evident that the components of the terminal receptor subgroups were similar to those found in the PAUP tree. These terminal clusters might then represent phylogenetically stable relationships. The positions of some orphan receptors were perturbed when a different algorithm was employed in the analysis. Both PAUP and N-J evolutionary trees showed that the receptors within the subgroups of a major sublineage tend to recognize hormones of very similar structure. This finding suggests that the relative phylogenetic position of orphans to well-characterized receptors might be exploited to predict the type of ligand they would recognize.

Algorithms↗
PubMed1993

Undermethylation of specific LINE-1 sequences in human cells producing a LINE-1-encoded protein.

Nucleotide sequences near the 5' ends of some long interspersed elements-1 (LINE-1) from Homo sapiens (L1Hs) are undermethylated in cell lines which produce a L1Hs-encoded protein. In contrast, these sequences are methylated in cell lines with little or no detectable L1Hs expression. The fact that the 5' end of L1Hs is differentially methylated in cells exhibiting different levels of L1Hs expression suggests that the methylation state of this region plays a role in L1Hs expression.

Blotting, Southern↗
PubMed1993

LINE-1 retrotransposon expression in pediatric germ cell tumors.

BACKGROUND: Human LINE-1 (L1Hs) is a retrotransposon that is known to cause insertion mutations. Previous work demonstrated that at least 10% of adult testicular germ cell cancers expressed the L1Hs element. METHODS: Pediatric germ cell tumors were assayed for L1Hs expression by in situ immunohistochemical methods using an antibody directed against one of the L1Hs-encoded proteins. RESULTS: Approximately 10% of pediatric germ cell tumors express abundant amounts of the L1Hs protein. The element was expressed in 1 of 19 ovarian tumors, 1 of 20 testicular tumors, and 4 of 19 extragonadal tumors. The reactive cells in all cases appeared to be embryonal carcinoma or yolk sac tumor cells. None of 32 ovarian immature teratomas gave positive results, suggesting that more differentiated tissues do not express L1Hs abundantly. CONCLUSIONS: It appears that neither the age nor sex of the patient, nor the location of the tumor, has a significant influence on the degree of L1Hs expression.

Adolescent↗
PubMed1993

Satellite DNA sequences in the New World primate Cebus apella Plaatyrrhini, Primates).

Two satellite DNAs, designated CapA and CapB, were isolated from the neotropical primate, Cebus apella. The satellites exhibit nonoverlapping distributions on C. apella chromosomes. CapA is a major component of interstitial regions of constitutive heterochromatin, a very large block of heterochromatin comprising most of the long arm of chromosome 11, and some telomeres. The CapA monomer has a length of about 1500 bp and appears recently to have undergone an amplification episode in the C. apella genome. CapA-like sequences are probably present in members of the family Cebidae (to which C. apella belongs), but not in members of the family Callitrichidae (marmosets). CapB sequences can be detected at the centromeres of many C. apella chromosomes, and similar sequences are present in all neotropical primates. The 342 bp CapB monomer shares 60%-64% sequence identity with several alpha satellite sequences of human origin. Because of its structure, sequence, and location, it appears that CapB is the New World primate homolog of Old World primate alpha satellite DNA.

Animals↗