Existing Host Range Mutations Constrain Further Emergence of RNA Viruses

ABSTRACTRNA viruses are capable of rapid host shifting, typically due to a point mutation that confers expanded host range. As additional point mutations are necessary for further expansions, epistasis among host range mutations can potentially affect the mutational neighborhood and frequency of niche expansion. We mapped the mutational neighborhood of host range expansion using three genotypes of the double-stranded RNA (dsRNA) bacteriophage φ6 (wild type and two isogenic host range mutants) on the novel hostPseudomonas syringaepv. atrofaciens. Both Sanger sequencing of 50P. syringaepv. atrofaciens mutant clones for each genotype and population Illumina sequencing revealed the same high-frequency mutations allowing infection ofP. syringaepv. atrofaciens. Wild-type φ6 had at least nine different ways of mutating to enter the novel host, eight of which are in p3 (host attachment protein gene), and 13/50 clones had unchanged p3 genes. However, the two isogenic mutants had dramatically restricted neighborhoods: only one or two mutations, all in p3. Deep sequencing revealed that wild-type clones without mutations in p3 likely had changes in p12 (morphogenic protein), a region that was not polymorphic for the two isogenic host range mutants. Sanger sequencing confirmed that 10/13 of the wild-type φ6 clones had nonsynonymous mutations in p12, and 2 others had point mutations in p9 and p5. None of these genes had previously been associated with host range expansion in φ6. We demonstrate, for the first time, epistatic constraint in an RNA virus due to host range mutations themselves, which has implications for models of serial host range expansion.IMPORTANCERNA viruses mutate rapidly and frequently expand their host ranges to infect novel hosts, leading to serial host shifts. Using an RNA bacteriophage model system (Pseudomonasphage φ6), we studied the impact of preexisting host range mutations on another host range expansion. Results from both clonal Sanger and Illumina sequencing show that extant host range mutations dramatically narrow the neighborhood of potential host range mutations compared to that of wild-type φ6. This research suggests that serial host-shifting viruses may follow a small number of molecular paths to enter additional novel hosts. We also identified new genes involved in φ6 host range expansion, expanding our knowledge of this important model system in experimental evolution.

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Existing host range mutations constrain further emergence of RNA viruses

10.1101/394080 ◽

2018 ◽

Cited By ~ 1

Author(s):

Lele Zhao ◽

Mansha Seth Pasricha ◽

Dragos Stemate ◽

Alvin Crespo-Bellido ◽

Jacqueline Gagnon ◽

...

Keyword(s):

Host Range ◽

Illumina Sequencing ◽

Range Expansion ◽

Sanger Sequencing ◽

Rna Viruses ◽

Point Mutations ◽

Model System ◽

The Novel ◽

Host Range Expansion ◽

Novel Host

AbstractRNA viruses are capable of rapid host shifting, typically due to a point mutation that confers expanded host range. As additional point mutations are necessary for further expansions, epistasis among host range mutations can potentially affect the mutational neighborhood and frequency of niche expansion. We mapped the mutational neighborhood of host range expansion using three genotypes of the dsRNA bacteriophage phi6 (wildtype and two isogenic host range mutants) on the novel hostPseudomonas syringaepv.atrofaciens(PA). Sanger sequencing of fifty PA mutant clones for each genotype and population Illumina sequencing both revealed the same high frequency mutations allowing infection of PA. Wildtype phi6 had at least nine different ways of mutating to enter the novel host, eight of which are in p3 (host attachment protein gene), and 13/50 clones had unchanged p3 genes. However, the two isogenic mutants had dramatically restricted neighborhoods: only one or two mutations, all in p3. Deep sequencing revealed that wildtype clones without mutations in p3 likely had changes in p12 (morphogenic protein), a region that was not polymorphic for the two isogenic host range mutants. Sanger sequencing confirmed that 10/13 of the wildtype phi6 clones had nonsynonymous mutations in p12 and two others had point mutations in p9 and p5 – none of these genes had previously been associated with host range expansion in phi6. We demonstrate, for the first time, epistatic constraint in an RNA virus due to host range mutations themselves, which has implications for models of serial host range expansion.ImportanceRNA viruses mutate rapidly and frequently expand their host ranges to infect novel hosts, leading to serial host shifts. Using an RNA bacteriophage model system (Pseudomonasphage phi6), we studied the impact of pre-existing host range mutations on another host range expansion. Results from both clonal Sanger and Illumina sequencing show extant host range mutations dramatically narrow the neighborhood of potential host range mutations compared to wildtype phi6. This research suggests that serial host shifting viruses may follow a small number of molecular paths to enter additional novel hosts. We also identified new genes involved in phi6 host range expansion, expanding our knowledge of this important model system in experimental evolution.

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Recessive Host Range Mutants and Unsusceptible Cells That Inactivate Virions without Genome Penetration: Ecological and Technical Implications

Journal of Virology ◽

10.1128/jvi.01767-18 ◽

2018 ◽

Vol 93 (3) ◽

Cited By ~ 1

Author(s):

Aaron P. Roznowski ◽

Robert J. Young ◽

Samuel D. Love ◽

Avenetti A. Andromita ◽

Vanessa A. Guzman ◽

...

Keyword(s):

Coat Protein ◽

Host Range ◽

Range Expansion ◽

Single Point ◽

Point Mutations ◽

Structural Data ◽

Viral Population ◽

Content Type ◽

Host Range Expansion ◽

K 12

ABSTRACTAlthough microviruses do not possess a visible tail structure, one vertex rearranges after interacting with host lipopolysaccharides. Most examinations of host range, eclipse, and penetration were conducted before this “host-induced” unique vertex was discovered and before DNA sequencing became routine. Consequently, structure-function relationships dictating host range remain undefined. Biochemical and genetic analyses were conducted with two closely related microviruses, α3 and ST-1. Despite ∼90% amino acid identity, the natural host of α3 isEscherichia coliC, whereas ST-1 is a K-12-specific phage. Virions attached and eclipsed to both native and unsusceptible hosts; however, they breached only the native host’s cell wall. This suggests that unsusceptible host-phage interactions promote off-pathway reactions that can inactivate viruses without penetration. This phenomenon may have broader ecological implications. To determine which structural proteins conferred host range specificity, chimeric virions were generated by individually interchanging the coat, spike, or DNA pilot proteins. Interchanging the coat protein switched host range. However, host range expansion could be conferred by single point mutations in the coat protein. The expansion phenotype was recessive: genetically mutant progeny from coinfected cells did not display the phenotype. Thus, mutant isolation required populations generated in environments with low multiplicities of infection (MOI), a phenomenon that may have impacted past host range studies in both prokaryotic and eukaryotic systems. The resulting genetic and structural data were consistent enough that host range expansion could be predicted, broadening the classical definition of antireceptors to include interfaces between protein complexes within the capsid.IMPORTANCETo expand host range, viruses must interact with unsusceptible host cell surfaces, which could be detrimental. As observed in this study, virions were inactivated without genome penetration. This may be advantageous to potential new hosts, culling the viral population from which an expanded host range mutant could emerge. When identified, altered host range mutations were recessive. Accordingly, isolation required populations generated in low-MOI environments. However, in laboratory settings, viral propagation includes high-MOI conditions. Typically, infected cultures incubate until all cells produce progeny. Thus, coinfections dominate later replication cycles, masking recessive host range expansion phenotypes. This may have impacted similar studies with other viruses. Last, structural and genetic data could be used to predict site-directed mutant phenotypes, which may broaden the classic antireceptor definition to include interfaces between capsid complexes.

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Oviposition of diamondback moth in the presence and absence of a novel host plant

Bulletin of Entomological Research ◽

10.1017/s0007485310000234 ◽

2010 ◽

Vol 101 (1) ◽

pp. 99-105 ◽

Cited By ~ 10

Author(s):

K. Henniges-Janssen ◽

G. Schöfl ◽

A. Reineke ◽

D.G. Heckel ◽

A.T. Groot

Keyword(s):

Host Range ◽

Larval Development ◽

Host Plant ◽

Plutella Xylostella ◽

Range Expansion ◽

Host Plants ◽

Diamondback Moth ◽

Host Range Expansion ◽

Cabbage Plant ◽

Novel Host

AbstractThe diamondback moth (DBM, Plutella xylostella L. (Lepidoptera: Plutellidae)) consumes a wide variety of brassicaceous host plants and is a common pest of crucifer crops worldwide. A highly unusual infestation of a sugar pea crop was recorded in Kenya in 1999, which persisted for two consecutive years. A strain (DBM-P) from this population was established in the laboratory and is the only one of several strains tested that can complete larval development on sugar peas. The oviposition acceptance and preference of the DBM-P strain was assessed in the presence of cabbage plants, sugar pea plants or both, in comparison to another strain (DBM-Cj) that was collected from cabbage and is unable to grow on pea plants. As expected, DBM-Cj females preferred to oviposit on cabbage plants. Surprisingly, DBM-P females also laid most eggs on cabbage and very few on peas. However, they laid significantly more eggs on the cabbage plant when pea plants were present. Our findings suggest that DBM-P manifested the initial stages of an evolutionary host range expansion, which is incomplete due to lack of oviposition fidelity on pea plants.

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Correlation of Host Range Expansion of Therapeutic Bacteriophage Sb-1 with Allele State at a Hypervariable Repeat Locus

Applied and Environmental Microbiology ◽

10.1128/aem.01209-19 ◽

2019 ◽

Vol 85 (22) ◽

Cited By ~ 11

Author(s):

Kirill V. Sergueev ◽

Andrey A. Filippov ◽

Jason Farlow ◽

Wanwen Su ◽

Leila Kvachadze ◽

...

Keyword(s):

Health Care ◽

Staphylococcus Aureus ◽

Host Range ◽

Range Expansion ◽

Genetic Basis ◽

Hypervariable Region ◽

Methicillin Resistant ◽

Content Type ◽

Host Range Expansion ◽

Distinct Allele

ABSTRACT Staphylococci are frequent agents of health care-associated infections and include methicillin-resistant Staphylococcus aureus (MRSA), which is resistant to first-line antibiotic treatments. Bacteriophage (phage) therapy is a promising alternative antibacterial option to treat MRSA infections. S. aureus-specific phage Sb-1 has been widely used in Georgia to treat a variety of human S. aureus infections. Sb-1 has a broad host range within S. aureus, including MRSA strains, and its host range can be further expanded by adaptation to previously resistant clinical isolates. The susceptibilities of a panel of 25 genetically diverse clinical MRSA isolates to Sb-1 phage were tested, and the phage had lytic activity against 23 strains (92%). The adapted phage stock (designated Sb-1A) was tested in comparison with the parental phage (designated Sb-1P). Sb-1P had lytic activity against 78/90 strains (87%) in an expanded panel of diverse global S. aureus isolates, while eight additional strains in this panel were susceptible to Sb-1A (lytic against 86/90 strains [96%]). The Sb-1A stock was shown to be a mixed population of phage clones, including approximately 4% expanded host range mutants, designated Sb-1M. In an effort to better understand the genetic basis for this host range expansion, we sequenced the complete genomes of the parental Sb-1P and two Sb-1M mutants. Comparative genomic analysis revealed a hypervariable complex repeat structure in the Sb-1 genome that had a distinct allele that correlated with the host range expansion. This hypervariable region was previously uncharacterized in Twort-like phages and represents a novel putative host range determinant. IMPORTANCE Because of limited therapeutic options, infections caused by methicillin-resistant Staphylococcus aureus represent a serious problem in both civilian and military health care settings. Phages have potential as alternative antibacterial agents that can be used in combination with antibiotic drugs. For decades, phage Sb-1 has been used in former Soviet Union countries for antistaphylococcal treatment in humans. The therapeutic spectrum of activity of Sb-1 can be increased by selecting mutants of the phage with expanded host ranges. In this work, the host range of phage Sb-1 was expanded in the laboratory, and a hypervariable region in its genome was identified with a distinct allele state that correlated with this host range expansion. These results provide a genetic basis for better understanding the mechanisms of phage host range expansion.

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Infestation of a novel host plant by Tephritis conura (Diptera: Tephritidae) in northern Britain: host-range expansion or host shift?

Genetica ◽

10.1007/s10709-009-9353-3 ◽

2009 ◽

Vol 137 (1) ◽

pp. 87-97 ◽

Cited By ~ 14

Author(s):

Thorsten Diegisser ◽

Christian Tritsch ◽

Alfred Seitz ◽

Jes Johannesen

Keyword(s):

Host Range ◽

Host Plant ◽

Range Expansion ◽

Host Shift ◽

Host Range Expansion ◽

Novel Host

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Host range expansion and the insect immune response

10.1603/ice.2016.93627 ◽

2016 ◽

Author(s):

Angela Smilanich

Keyword(s):

Immune Response ◽

Host Range ◽

Range Expansion ◽

Host Range Expansion ◽

Insect Immune Response

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Golovinomyces longipes (Noordel. & Loer.) L. Kiss on Matricaria chamomilla L.: another host range expansion

Journal of Plant Diseases and Protection ◽

10.1007/s41348-021-00512-4 ◽

2021 ◽

Author(s):

M. Götz ◽

U. Braun

Keyword(s):

Sequence Analysis ◽

Powdery Mildew ◽

Host Range ◽

Dna Sequence ◽

Range Expansion ◽

Matricaria Chamomilla ◽

Important Family ◽

The Past ◽

Morphological Studies ◽

Host Range Expansion

AbstractGolovinomyces longipes is a widespread powdery mildew on Solanaceae (Nicotiana, Petunia and Solanum spp.). In the past, it has been reported only once on Verbena (Verbenaceae), a non-solanaceaous host. Recently, this powdery mildew has been found on the composite Matricaria chamomilla. The identification of the powdery mildew species on this unusual host has been proved by morphological studies and DNA sequence analysis. Both datasets coincide with the characteristic data for G. longipes on Solanaceae. First inoculation experiments with further composites resulted in an infection of Brachyscome hybrid ‘Surdaisy’. To our knowledge, this is the first report of G. lonigpes on hosts belonging to the important family of Asteraceae and an additional proof of the broader host range of G. longipes beyond the Solanaceae.

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