Transferrin receptor binds virus capsid with dynamic motion

Lee, Hyunwook; Callaway, Heather; Cifuente, Javier O.; Bator, Carol M.; Parrish, Colin R.; Hafenstein, Susan

doi:10.1073/pnas.1904918116

Cited by 32 publications

(23 citation statements)

References 68 publications

(105 reference statements)

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“…This may result in a change to the molecular surface of the core of the receptor-binding region, subsequently influencing receptor-binding affinity between the transferrin receptor and the virus. In addition, our data agree with previous studies indicating that residue 101 is located not only at the core of the receptor-binding region (Lee et al, 2019) but also at the antibody-binding site (Organtini et al, 2016). Taken together, the impact of the Thr101 mutation will require further investigation.…”

Section: Discussionsupporting

confidence: 91%

Genetic characterization of feline panleukopenia virus from dogs in Vietnam reveals a unique Thr101 mutation in VP2

Hoang

Lin

et al. 2020

PeerJ

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Background Canine parvovirus type 2 (CPV-2) and feline parvovirus (FPV) are known as the main causes of several serious diseases and have a severe impact on puppies and kittens, respectively. FPV and new CPV-2 variants are all able to infect cats, causing diseases indistinguishable from feline panleukopenia. However, FPV only replicates efficiently in feline cells in vitro and replicates in dogs in the thymus and bone marrow without being shed in feces. In our previous study, the genotypes of six parvoviral isolates were unable to be identified using a SimpleProbe® real-time PCR assay. Methods In the present study, we characterized previously unidentified FPV-like viruses isolated from dogs in Vietnam. The six isolates were utilized to complete VP2 gene sequencing and to conduct phylogenetic analyses. Results Sequence analysis of the six parvoviral strains identified the species as being similar to FPV. Phylogenetic analysis demonstrated that the complete VP2 genes of the strains are similar to those of FPV. The FPV-like strains contain a Thr101 mutation in the VP2 protein, which is different from prototype FPV strains. Discussion Our data provide evidence for the existence of changes in the charge, protein contact potential and molecular surface of the core of the receptor-binding size with an Ile101 to Thr101 mutation. This is also the first study to provide reliable evidence that FPV may be a threat to the Vietnamese dog population.

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Section: Discussionsupporting

confidence: 91%

Genetic characterization of feline panleukopenia virus from dogs in Vietnam reveals a unique Thr101 mutation in VP2

Hoang

Lin

et al. 2020

PeerJ

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“…Viruses classified within the same Baltimore group can use the same receptors for cell infection, which is in contrast with our canonical understanding that identical entry receptors are utilized by viruses from the same taxonomic family (e.g. TfR is utilized by members of the Parvoviridae family such as FPV and CPV during infection (Lofling et al 2013;Lee et al 2019). Take TfR as an example, the PCV, which belongs to the Circoviridae family, shares the same Baltimore group II with the CPV that also uses TfR as the receptor (Misinzo 2005).…”

Section: Opportunities and Challengesmentioning

confidence: 86%

Host receptors: the key to establishing cells with broad viral tropism for vaccine production

Dai

Zhang

Ostrikov

et al. 2020

Critical Reviews in Microbiology

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Cell culture-based vaccine technology is a flexible and convenient approach for vaccine production that requires adaptation of the vaccine strains to the new cells. Driven by the motivation to develop a broadly permissive cell line for infection with a wide range of viruses, we identified a set of the most relevant host receptors involved in viral attachment and entry. This identification was done through a review of different viral entry pathways and host cell lines, and in the context of the Baltimore classification of viruses. In addition, we indicated the potential technical problems and proposed some solutions regarding how to modify the host cell genome in order to meet industrial requirements for mass production of antiviral vaccines. Our work contributes to a finer understanding of the importance of breaking the host-virus recognition specificities for the possibility of creating a cell line feasible for the production of vaccines against a broad spectrum of viruses. ARTICLE HISTORY

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“…It falls within a region of the capsid structure that stabilizes a loop containing VP2 residues 300 and 301, which interact directly with the TfR (Fig. 7B) (30). By removing a hydrogen bond interacting with this loop, the VP2 Arg81Thr substitution likely permits greater flexibility of the capsid.…”

Section: Figmentioning

confidence: 99%

“…Such mutations likely reflect adaptation of the viruses in overcoming host barriers to infection or optimizing their interactions with TfR binding sites (19). Recently, the TfR-CPV interaction has been further defined using cryo-electron microscopy (cryoEM) (30), providing atomic resolution structural information of the viral capsid-host cell receptor interface.…”

mentioning

confidence: 99%

Limited Intrahost Diversity and Background Evolution Accompany 40 Years of Canine Parvovirus Host Adaptation and Spread

Voorhees

Lee

Allison

et al. 2019

J Virol

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Canine parvovirus (CPV) is a highly successful pathogen that has sustained pandemic circulation in dogs for more than 40 years. Here, integrating full-genome and deep-sequencing analyses, structural information, and in vitro experimentation, we describe the macro- and microscale features that accompany CPV’s evolutionary success. Despite 40 years of viral evolution, all CPV variants are more than ∼99% identical in nucleotide sequence, with only a limited number (<40) of substitutions becoming fixed or widespread during this time. Notably, most substitutions in the major capsid protein (VP2) gene are nonsynonymous, altering amino acid residues that fall within, or adjacent to, the overlapping receptor footprint or antigenic regions, suggesting that natural selection has channeled much of CPV evolution. Among the limited number of variable sites, CPV genomes exhibit complex patterns of variation that include parallel evolution, reversion, and recombination, compromising phylogenetic inference. At the intrahost level, deep sequencing of viral DNA in original clinical samples from dogs and other host species sampled between 1978 and 2018 revealed few subconsensus single nucleotide variants (SNVs) above ∼0.5%, and experimental passages demonstrate that substantial preexisting genetic variation is not necessarily required for rapid host receptor-driven adaptation. Together, these findings suggest that although CPV is capable of rapid host adaptation, a relatively low mutation rate, pleiotropy, and/or a lack of selective challenges since its initial emergence have inhibited the long-term accumulation of genetic diversity. Hence, continuously high levels of inter- and intrahost diversity are not necessarily required for virus host adaptation. IMPORTANCE Rapid mutation rates and correspondingly high levels of intra- and interhost diversity are often cited as key features of viruses with the capacity for emergence and sustained transmission in a new host species. However, most of this information comes from studies of RNA viruses, with relatively little known about evolutionary processes in viruses with single-stranded DNA (ssDNA) genomes. Here, we provide a unique model of virus evolution, integrating both long-term global-scale and short-term intrahost evolutionary processes of an ssDNA virus that emerged to cause a pandemic in a new host animal. Our analysis reveals that successful host jumping and sustained transmission does not necessarily depend on a high level of intrahost diversity nor result in the continued accumulation of high levels of long-term evolution change. These findings indicate that all aspects of the biology and ecology of a virus are relevant when considering their adaptability.

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Transferrin receptor binds virus capsid with dynamic motion

Cited by 32 publications

References 68 publications

Genetic characterization of feline panleukopenia virus from dogs in Vietnam reveals a unique Thr101 mutation in VP2

Genetic characterization of feline panleukopenia virus from dogs in Vietnam reveals a unique Thr101 mutation in VP2

Host receptors: the key to establishing cells with broad viral tropism for vaccine production

Limited Intrahost Diversity and Background Evolution Accompany 40 Years of Canine Parvovirus Host Adaptation and Spread

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