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Andrew E Firth - One of the best experts on this subject based on the ideXlab platform.
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Ribosomal frameshifting into an Overlapping Gene in the 2B-encoding region of the cardiovirus genome.
Proceedings of the National Academy of Sciences of the United States of America, 2011Co-Authors: Gary Loughran, Andrew E Firth, John F. AtkinsAbstract:The genus Cardiovirus (family Picornaviridae) currently comprises the species Encephalomyocarditis virus (EMCV) and Theilovirus. Cardioviruses have a positive-sense, single-stranded RNA genome that encodes a large polyprotein (L-1ABCD-2ABC-3ABCD) that is cleaved to produce approximately 12 mature proteins. We report on a conserved ORF that overlaps the 2B-encoding sequence of EMCV in the +2 reading frame. The ORF is translated as a 128-129 amino acid transframe fusion (2B*) with the N-terminal 11-12 amino acids of 2B, via ribosomal frameshifting at a conserved GGUUUUY motif. Mutations that knock out expression of 2B* result in a small-plaque phenotype. Curiously, although theilovirus sequences lack a long ORF in the +2 frame at this genomic location, they maintain a conserved GGUUUUU motif just downstream of the 2A-2B junction, and a highly localized peak in conservation at polyprotein-frame synonymous sites suggests that theiloviruses also utilize frameshifting here, albeit into a very short +2-frame ORF. Unlike previous cases of programmed -1 frameshifting, here frameshifting is modulated by virus infection, thus suggesting a novel regulatory role for frameshifting in these viruses.
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Candidates in Astroviruses, Seadornaviruses, Cytorhabdoviruses and Coronaviruses for +1 frame Overlapping Genes accessed by leaky scanning
Virology Journal, 2010Co-Authors: Andrew E Firth, John F. AtkinsAbstract:Background Overlapping Genes are common in RNA viruses where they serve as a mechanism to optimize the coding potential of compact genomes. However, annotation of Overlapping Genes can be difficult using conventional Gene-finding software. Recently we have been using a number of complementary approaches to systematically identify previously undetected Overlapping Genes in RNA virus genomes. In this article we gather together a number of promising candidate new Overlapping Genes that may be of interest to the community. Results Overlapping Gene predictions are presented for the astroviruses, seadornaviruses, cytorhabdoviruses and coronaviruses (families Astroviridae , Reoviridae , Rhabdoviridae and Coronaviridae , respectively).
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Evidence for ribosomal frameshifting and a novel Overlapping Gene in the genomes of insect-specific flaviviruses.
Virology, 2010Co-Authors: Andrew E Firth, Bradley J. Blitvich, Norma M. Wills, Cathy L. Miller, John F. AtkinsAbstract:Flaviviruses have a positive-sense, single-stranded RNA genome of approximately 11 kb, encoding a large polyprotein that is cleaved to produce approximately 10 mature proteins. Cell fusing agent virus, Kamiti River virus, Culex flavivirus and several recently discovered flaviviruses have no known vertebrate host and apparently infect only insects. We present compelling bioinformatic evidence for a 253-295 codon Overlapping Gene (designated fifo) conserved throughout these insect-specific flaviviruses and immunofluorescent detection of its product. Fifo overlaps the NS2A/NS2B coding sequence in the -1/+2 reading frame and is most likely expressed as a trans-frame fusion protein via ribosomal frameshifting at a conserved GGAUUUY slippery heptanucleotide with 3'-adjacent RNA secondary structure (which stimulates efficient frameshifting in vitro). The discovery bears striking parallels to the recently discovered ribosomal frameshifting site in the NS2A coding sequence of the Japanese encephalitis serogroup of flaviviruses and suggests that programmed ribosomal frameshifting may be more widespread in flaviviruses than currently realized.
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Bioinformatic evidence for a stem-loop structure 5'-adjacent to the IGR-IRES and for an Overlapping Gene in the bee paralysis dicistroviruses
Virology Journal, 2009Co-Authors: Andrew E Firth, Qing S. Wang, John F. AtkinsAbstract:The family Dicistroviridae (order Picornavirales) includes species that infect insects and other arthropods. These viruses have a linear positive-sense ssRNA genome of ~8-10 kb, which contains two long ORFs. The 5' ORF encodes the nonstructural polyprotein while the 3' ORF encodes the structural polyprotein. The dicistroviruses are noteworthy for the intergenic Internal Ribosome Entry Site (IGR-IRES) that mediates efficient translation initation on the 3' ORF without the requirement for initiator Met-tRNA. Acute bee paralysis virus, Israel acute paralysis virus of bees and Kashmir bee virus form a distinct subgroup within the Dicistroviridae family. In this brief report, we describe the bioinformatic discovery of a new, apparently coding, ORF in these viruses. The ORF overlaps the 5' end of the structural polyprotein coding sequence in the +1 reading frame. We also identify a potential 14-18 bp RNA stem-loop structure 5'-adjacent to the IGR-IRES. We discuss potential translation initiation mechanisms for the novel ORF in the context of the IGR-IRES and 5'-adjacent stem-loop.
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Bioinformatic analysis suggests that a conserved ORF in the waikaviruses encodes an Overlapping Gene
Archives of Virology, 2008Co-Authors: Andrew E Firth, John F. AtkinsAbstract:The genus Waikavirus belongs to the order Picornavirales , whose members all use a polyprotein expression strategy. With the exception of Theiler’s virus, Overlapping Genes are essentially unknown in the order. Recently, we reported experimental verification for a new short Overlapping coding sequence (CDS) in the Potyviridae —a family in which Overlapping Genes were previously unknown. Using the same bioinformatics software (MLOGD), we have identified an ~89-codon conserved open reading frame (ORF) with a strong coding signature in members of the genus Waikavirus . The ORF overlaps the polyprotein ORF but is in the +1 reading frame. Here, we describe the bioinformatic analysis.
John F. Atkins - One of the best experts on this subject based on the ideXlab platform.
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Ribosomal frameshifting into an Overlapping Gene in the 2B-encoding region of the cardiovirus genome.
Proceedings of the National Academy of Sciences of the United States of America, 2011Co-Authors: Gary Loughran, Andrew E Firth, John F. AtkinsAbstract:The genus Cardiovirus (family Picornaviridae) currently comprises the species Encephalomyocarditis virus (EMCV) and Theilovirus. Cardioviruses have a positive-sense, single-stranded RNA genome that encodes a large polyprotein (L-1ABCD-2ABC-3ABCD) that is cleaved to produce approximately 12 mature proteins. We report on a conserved ORF that overlaps the 2B-encoding sequence of EMCV in the +2 reading frame. The ORF is translated as a 128-129 amino acid transframe fusion (2B*) with the N-terminal 11-12 amino acids of 2B, via ribosomal frameshifting at a conserved GGUUUUY motif. Mutations that knock out expression of 2B* result in a small-plaque phenotype. Curiously, although theilovirus sequences lack a long ORF in the +2 frame at this genomic location, they maintain a conserved GGUUUUU motif just downstream of the 2A-2B junction, and a highly localized peak in conservation at polyprotein-frame synonymous sites suggests that theiloviruses also utilize frameshifting here, albeit into a very short +2-frame ORF. Unlike previous cases of programmed -1 frameshifting, here frameshifting is modulated by virus infection, thus suggesting a novel regulatory role for frameshifting in these viruses.
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Candidates in Astroviruses, Seadornaviruses, Cytorhabdoviruses and Coronaviruses for +1 frame Overlapping Genes accessed by leaky scanning
Virology Journal, 2010Co-Authors: Andrew E Firth, John F. AtkinsAbstract:Background Overlapping Genes are common in RNA viruses where they serve as a mechanism to optimize the coding potential of compact genomes. However, annotation of Overlapping Genes can be difficult using conventional Gene-finding software. Recently we have been using a number of complementary approaches to systematically identify previously undetected Overlapping Genes in RNA virus genomes. In this article we gather together a number of promising candidate new Overlapping Genes that may be of interest to the community. Results Overlapping Gene predictions are presented for the astroviruses, seadornaviruses, cytorhabdoviruses and coronaviruses (families Astroviridae , Reoviridae , Rhabdoviridae and Coronaviridae , respectively).
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Evidence for ribosomal frameshifting and a novel Overlapping Gene in the genomes of insect-specific flaviviruses.
Virology, 2010Co-Authors: Andrew E Firth, Bradley J. Blitvich, Norma M. Wills, Cathy L. Miller, John F. AtkinsAbstract:Flaviviruses have a positive-sense, single-stranded RNA genome of approximately 11 kb, encoding a large polyprotein that is cleaved to produce approximately 10 mature proteins. Cell fusing agent virus, Kamiti River virus, Culex flavivirus and several recently discovered flaviviruses have no known vertebrate host and apparently infect only insects. We present compelling bioinformatic evidence for a 253-295 codon Overlapping Gene (designated fifo) conserved throughout these insect-specific flaviviruses and immunofluorescent detection of its product. Fifo overlaps the NS2A/NS2B coding sequence in the -1/+2 reading frame and is most likely expressed as a trans-frame fusion protein via ribosomal frameshifting at a conserved GGAUUUY slippery heptanucleotide with 3'-adjacent RNA secondary structure (which stimulates efficient frameshifting in vitro). The discovery bears striking parallels to the recently discovered ribosomal frameshifting site in the NS2A coding sequence of the Japanese encephalitis serogroup of flaviviruses and suggests that programmed ribosomal frameshifting may be more widespread in flaviviruses than currently realized.
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Bioinformatic evidence for a stem-loop structure 5'-adjacent to the IGR-IRES and for an Overlapping Gene in the bee paralysis dicistroviruses
Virology Journal, 2009Co-Authors: Andrew E Firth, Qing S. Wang, John F. AtkinsAbstract:The family Dicistroviridae (order Picornavirales) includes species that infect insects and other arthropods. These viruses have a linear positive-sense ssRNA genome of ~8-10 kb, which contains two long ORFs. The 5' ORF encodes the nonstructural polyprotein while the 3' ORF encodes the structural polyprotein. The dicistroviruses are noteworthy for the intergenic Internal Ribosome Entry Site (IGR-IRES) that mediates efficient translation initation on the 3' ORF without the requirement for initiator Met-tRNA. Acute bee paralysis virus, Israel acute paralysis virus of bees and Kashmir bee virus form a distinct subgroup within the Dicistroviridae family. In this brief report, we describe the bioinformatic discovery of a new, apparently coding, ORF in these viruses. The ORF overlaps the 5' end of the structural polyprotein coding sequence in the +1 reading frame. We also identify a potential 14-18 bp RNA stem-loop structure 5'-adjacent to the IGR-IRES. We discuss potential translation initiation mechanisms for the novel ORF in the context of the IGR-IRES and 5'-adjacent stem-loop.
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Bioinformatic analysis suggests that a conserved ORF in the waikaviruses encodes an Overlapping Gene
Archives of Virology, 2008Co-Authors: Andrew E Firth, John F. AtkinsAbstract:The genus Waikavirus belongs to the order Picornavirales , whose members all use a polyprotein expression strategy. With the exception of Theiler’s virus, Overlapping Genes are essentially unknown in the order. Recently, we reported experimental verification for a new short Overlapping coding sequence (CDS) in the Potyviridae —a family in which Overlapping Genes were previously unknown. Using the same bioinformatics software (MLOGD), we have identified an ~89-codon conserved open reading frame (ORF) with a strong coding signature in members of the genus Waikavirus . The ORF overlaps the polyprotein ORF but is in the +1 reading frame. Here, we describe the bioinformatic analysis.
Christoph Lippuner - One of the best experts on this subject based on the ideXlab platform.
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asexual expansion of toxoplasma gondii merozoites is distinct from tachyzoites and entails expression of non Overlapping Gene families to attach invade and replicate within feline enterocytes
BMC Genomics, 2015Co-Authors: Adrian B Hehl, Walter Basso, Christoph Lippuner, Chandra Ramakrishnan, Michal J Okoniewski, Robert A Walker, Michael E Grigg, Nicholas SmithAbstract:The apicomplexan parasite Toxoplasma gondii is cosmopolitan in nature, largely as a result of its highly flexible life cycle. Felids are its only definitive hosts and a wide range of mammals and birds serve as intermediate hosts. The latent bradyzoite stage is orally infectious in all warm-blooded vertebrates and establishes chronic, transmissible infections. When bradyzoites are ingested by felids, they transform into merozoites in enterocytes and expand asexually as part of their coccidian life cycle. In all other intermediate hosts, however, bradyzoites differentiate exclusively to tachyzoites, and disseminate extraintestinally to many cell types. Both merozoites and tachyzoites undergo rapid asexual population expansion, yet possess different effector fates with respect to the cells and tissues they develop in and the subsequent stages they differentiate into. To determine whether merozoites utilize distinct suites of Genes to attach, invade, and replicate within feline enterocytes, we performed comparative transcriptional profiling on purified tachyzoites and merozoites. We used high-throughput RNA-Seq to compare the merozoite and tachyzoite transcriptomes. 8323 Genes were annotated with sequence reads across the two asexually replicating stages of the parasite life cycle. Metabolism was similar between the two replicating stages. However, significant stage-specific expression differences were measured, with 312 transcripts exclusive to merozoites versus 453 exclusive to tachyzoites. Genes coding for 177 predicted secreted proteins and 64 membrane- associated proteins were annotated as merozoite-specific. The vast majority of known dense-granule (GRA), microneme (MIC), and rhoptry (ROP) Genes were not expressed in merozoites. In contrast, a large set of surface proteins (SRS) was expressed exclusively in merozoites. The distinct expression profiles of merozoites and tachyzoites reveal significant additional complexity within the T. gondii life cycle, demonstrating that merozoites are distinct asexual dividing stages which are uniquely adapted to their niche and biological purpose.
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Asexual expansion of Toxoplasma gondii merozoites is distinct from tachyzoites and entails expression of non-Overlapping Gene families to attach, invade, and replicate within feline enterocytes
BMC Genomics, 2015Co-Authors: Adrian B Hehl, Christoph Lippuner, Chandra Ramakrishnan, Michal J Okoniewski, Robert A Walker, Michael E Grigg, Walter U Basso, Nicholas C Smith, Peter DeplazesAbstract:Background The apicomplexan parasite Toxoplasma gondii is cosmopolitan in nature, largely as a result of its highly flexible life cycle. Felids are its only definitive hosts and a wide range of mammals and birds serve as intermediate hosts. The latent bradyzoite stage is orally infectious in all warm-blooded vertebrates and establishes chronic, transmissible infections. When bradyzoites are ingested by felids, they transform into merozoites in enterocytes and expand asexually as part of their coccidian life cycle. In all other intermediate hosts, however, bradyzoites differentiate exclusively to tachyzoites, and disseminate extraintestinally to many cell types. Both merozoites and tachyzoites undergo rapid asexual population expansion, yet possess different effector fates with respect to the cells and tissues they develop in and the subsequent stages they differentiate into. Results To determine whether merozoites utilize distinct suites of Genes to attach, invade, and replicate within feline enterocytes, we performed comparative transcriptional profiling on purified tachyzoites and merozoites. We used high-throughput RNA-Seq to compare the merozoite and tachyzoite transcriptomes. 8323 Genes were annotated with sequence reads across the two asexually replicating stages of the parasite life cycle. Metabolism was similar between the two replicating stages. However, significant stage-specific expression differences were measured, with 312 transcripts exclusive to merozoites versus 453 exclusive to tachyzoites. Genes coding for 177 predicted secreted proteins and 64 membrane- associated proteins were annotated as merozoite-specific. The vast majority of known dense-granule ( GRA ), microneme ( MIC ), and rhoptry ( ROP ) Genes were not expressed in merozoites. In contrast, a large set of surface proteins (SRS) was expressed exclusively in merozoites. Conclusions The distinct expression profiles of merozoites and tachyzoites reveal significant additional complexity within the T. gondii life cycle, demonstrating that merozoites are distinct asexual dividing stages which are uniquely adapted to their niche and biological purpose.
Robert A Walker - One of the best experts on this subject based on the ideXlab platform.
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asexual expansion of toxoplasma gondii merozoites is distinct from tachyzoites and entails expression of non Overlapping Gene families to attach invade and replicate within feline enterocytes
BMC Genomics, 2015Co-Authors: Adrian B Hehl, Walter Basso, Christoph Lippuner, Chandra Ramakrishnan, Michal J Okoniewski, Robert A Walker, Michael E Grigg, Nicholas SmithAbstract:The apicomplexan parasite Toxoplasma gondii is cosmopolitan in nature, largely as a result of its highly flexible life cycle. Felids are its only definitive hosts and a wide range of mammals and birds serve as intermediate hosts. The latent bradyzoite stage is orally infectious in all warm-blooded vertebrates and establishes chronic, transmissible infections. When bradyzoites are ingested by felids, they transform into merozoites in enterocytes and expand asexually as part of their coccidian life cycle. In all other intermediate hosts, however, bradyzoites differentiate exclusively to tachyzoites, and disseminate extraintestinally to many cell types. Both merozoites and tachyzoites undergo rapid asexual population expansion, yet possess different effector fates with respect to the cells and tissues they develop in and the subsequent stages they differentiate into. To determine whether merozoites utilize distinct suites of Genes to attach, invade, and replicate within feline enterocytes, we performed comparative transcriptional profiling on purified tachyzoites and merozoites. We used high-throughput RNA-Seq to compare the merozoite and tachyzoite transcriptomes. 8323 Genes were annotated with sequence reads across the two asexually replicating stages of the parasite life cycle. Metabolism was similar between the two replicating stages. However, significant stage-specific expression differences were measured, with 312 transcripts exclusive to merozoites versus 453 exclusive to tachyzoites. Genes coding for 177 predicted secreted proteins and 64 membrane- associated proteins were annotated as merozoite-specific. The vast majority of known dense-granule (GRA), microneme (MIC), and rhoptry (ROP) Genes were not expressed in merozoites. In contrast, a large set of surface proteins (SRS) was expressed exclusively in merozoites. The distinct expression profiles of merozoites and tachyzoites reveal significant additional complexity within the T. gondii life cycle, demonstrating that merozoites are distinct asexual dividing stages which are uniquely adapted to their niche and biological purpose.
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Asexual expansion of Toxoplasma gondii merozoites is distinct from tachyzoites and entails expression of non-Overlapping Gene families to attach, invade, and replicate within feline enterocytes
BMC Genomics, 2015Co-Authors: Adrian B Hehl, Christoph Lippuner, Chandra Ramakrishnan, Michal J Okoniewski, Robert A Walker, Michael E Grigg, Walter U Basso, Nicholas C Smith, Peter DeplazesAbstract:Background The apicomplexan parasite Toxoplasma gondii is cosmopolitan in nature, largely as a result of its highly flexible life cycle. Felids are its only definitive hosts and a wide range of mammals and birds serve as intermediate hosts. The latent bradyzoite stage is orally infectious in all warm-blooded vertebrates and establishes chronic, transmissible infections. When bradyzoites are ingested by felids, they transform into merozoites in enterocytes and expand asexually as part of their coccidian life cycle. In all other intermediate hosts, however, bradyzoites differentiate exclusively to tachyzoites, and disseminate extraintestinally to many cell types. Both merozoites and tachyzoites undergo rapid asexual population expansion, yet possess different effector fates with respect to the cells and tissues they develop in and the subsequent stages they differentiate into. Results To determine whether merozoites utilize distinct suites of Genes to attach, invade, and replicate within feline enterocytes, we performed comparative transcriptional profiling on purified tachyzoites and merozoites. We used high-throughput RNA-Seq to compare the merozoite and tachyzoite transcriptomes. 8323 Genes were annotated with sequence reads across the two asexually replicating stages of the parasite life cycle. Metabolism was similar between the two replicating stages. However, significant stage-specific expression differences were measured, with 312 transcripts exclusive to merozoites versus 453 exclusive to tachyzoites. Genes coding for 177 predicted secreted proteins and 64 membrane- associated proteins were annotated as merozoite-specific. The vast majority of known dense-granule ( GRA ), microneme ( MIC ), and rhoptry ( ROP ) Genes were not expressed in merozoites. In contrast, a large set of surface proteins (SRS) was expressed exclusively in merozoites. Conclusions The distinct expression profiles of merozoites and tachyzoites reveal significant additional complexity within the T. gondii life cycle, demonstrating that merozoites are distinct asexual dividing stages which are uniquely adapted to their niche and biological purpose.
Adrian B Hehl - One of the best experts on this subject based on the ideXlab platform.
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asexual expansion of toxoplasma gondii merozoites is distinct from tachyzoites and entails expression of non Overlapping Gene families to attach invade and replicate within feline enterocytes
BMC Genomics, 2015Co-Authors: Adrian B Hehl, Walter Basso, Christoph Lippuner, Chandra Ramakrishnan, Michal J Okoniewski, Robert A Walker, Michael E Grigg, Nicholas SmithAbstract:The apicomplexan parasite Toxoplasma gondii is cosmopolitan in nature, largely as a result of its highly flexible life cycle. Felids are its only definitive hosts and a wide range of mammals and birds serve as intermediate hosts. The latent bradyzoite stage is orally infectious in all warm-blooded vertebrates and establishes chronic, transmissible infections. When bradyzoites are ingested by felids, they transform into merozoites in enterocytes and expand asexually as part of their coccidian life cycle. In all other intermediate hosts, however, bradyzoites differentiate exclusively to tachyzoites, and disseminate extraintestinally to many cell types. Both merozoites and tachyzoites undergo rapid asexual population expansion, yet possess different effector fates with respect to the cells and tissues they develop in and the subsequent stages they differentiate into. To determine whether merozoites utilize distinct suites of Genes to attach, invade, and replicate within feline enterocytes, we performed comparative transcriptional profiling on purified tachyzoites and merozoites. We used high-throughput RNA-Seq to compare the merozoite and tachyzoite transcriptomes. 8323 Genes were annotated with sequence reads across the two asexually replicating stages of the parasite life cycle. Metabolism was similar between the two replicating stages. However, significant stage-specific expression differences were measured, with 312 transcripts exclusive to merozoites versus 453 exclusive to tachyzoites. Genes coding for 177 predicted secreted proteins and 64 membrane- associated proteins were annotated as merozoite-specific. The vast majority of known dense-granule (GRA), microneme (MIC), and rhoptry (ROP) Genes were not expressed in merozoites. In contrast, a large set of surface proteins (SRS) was expressed exclusively in merozoites. The distinct expression profiles of merozoites and tachyzoites reveal significant additional complexity within the T. gondii life cycle, demonstrating that merozoites are distinct asexual dividing stages which are uniquely adapted to their niche and biological purpose.
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Asexual expansion of Toxoplasma gondii merozoites is distinct from tachyzoites and entails expression of non-Overlapping Gene families to attach, invade, and replicate within feline enterocytes
BMC Genomics, 2015Co-Authors: Adrian B Hehl, Christoph Lippuner, Chandra Ramakrishnan, Michal J Okoniewski, Robert A Walker, Michael E Grigg, Walter U Basso, Nicholas C Smith, Peter DeplazesAbstract:Background The apicomplexan parasite Toxoplasma gondii is cosmopolitan in nature, largely as a result of its highly flexible life cycle. Felids are its only definitive hosts and a wide range of mammals and birds serve as intermediate hosts. The latent bradyzoite stage is orally infectious in all warm-blooded vertebrates and establishes chronic, transmissible infections. When bradyzoites are ingested by felids, they transform into merozoites in enterocytes and expand asexually as part of their coccidian life cycle. In all other intermediate hosts, however, bradyzoites differentiate exclusively to tachyzoites, and disseminate extraintestinally to many cell types. Both merozoites and tachyzoites undergo rapid asexual population expansion, yet possess different effector fates with respect to the cells and tissues they develop in and the subsequent stages they differentiate into. Results To determine whether merozoites utilize distinct suites of Genes to attach, invade, and replicate within feline enterocytes, we performed comparative transcriptional profiling on purified tachyzoites and merozoites. We used high-throughput RNA-Seq to compare the merozoite and tachyzoite transcriptomes. 8323 Genes were annotated with sequence reads across the two asexually replicating stages of the parasite life cycle. Metabolism was similar between the two replicating stages. However, significant stage-specific expression differences were measured, with 312 transcripts exclusive to merozoites versus 453 exclusive to tachyzoites. Genes coding for 177 predicted secreted proteins and 64 membrane- associated proteins were annotated as merozoite-specific. The vast majority of known dense-granule ( GRA ), microneme ( MIC ), and rhoptry ( ROP ) Genes were not expressed in merozoites. In contrast, a large set of surface proteins (SRS) was expressed exclusively in merozoites. Conclusions The distinct expression profiles of merozoites and tachyzoites reveal significant additional complexity within the T. gondii life cycle, demonstrating that merozoites are distinct asexual dividing stages which are uniquely adapted to their niche and biological purpose.
