The genomes of three North American orthopoxviruses

Smithson, Chad; Tang, Nick C.; Sammons, Scott; Frace, Mike; Batra, Dhwani; Liu, Yu; Emerson, Ginny L.; Carroll, Darin S.; Upton, Chris

doi:10.1007/s11262-016-1388-9

Cited by 15 publications

(18 citation statements)

References 39 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…For instance, the predicted EKPV-NSW ORF048 gene which returned an unexpected weak similarity to a bacterium ( Microcystis aeruginosa ) hypothetical protein, whereas the ORF052 showed very low similarity with the hypothetical protein of pectate lyase of Paenibacillus sp (Supplementary Table S1 ). Furthermore, the EKPV-NSW ORF163 is most likely of eukaryotic origin considering the significant BALSTP scores against a eukaryotic ( Elephantulus edwardii ) 3-beta-hydroxysteroid dehydrogenase, although this catalytic enzyme recently been identified in several poxviruses such as skunkpox, volepox, and raccoonpox 36 . This may suggest that the members of the family poxvirus may carry these eukaryotic and or bacterial genes simply as poxviruses are more effective in capturing or maintaining host genes.…”

Section: Discussionmentioning

confidence: 99%

RETRACTED ARTICLE: Molecular and microscopic characterization of a novel Eastern grey kangaroopox virus genome directly from a clinical sample

Sarker

Roberts

Tidd

et al. 2017

Sci Rep

View full text Add to dashboard Cite

Poxviruses are large DNA viruses with varying zoonotic potential, and are recognised in a broad range of wildlife. Although poxviruses have been detected in kangaroos, their genetic relationships to poxviruses in other animals and humans is not well understood. Here, we present a novel genome sequence of a marsupial poxvirus, the Eastern grey kangaroopox virus (EKPV-NSW), isolated from a wild eastern grey kangaroo. In the present study, histopathologically confirmed epidermal pox lesions were used to recover the full-length viral genome and perform electron microscopic analysis, with both immature virions and intracellular mature virions detected. Subsequent analysis of the EKPV-NSW genome demonstrated the highest degree of sequence similarity with EKPV-SC strain (91.51%), followed by WKPV-WA (87.93%), and MOCV1 (44.05%). The novel EKPV-NSW complete genome encompasses most of the chordopoxviruses protein coding genes (138) that are required for genome replication and expression, with only three essential protein coding genes being absent. The novel EKPV-NSW is missing 28 predicted genes compared to the recently isolated EKPV-SC, and carries 21 additional unique genes, encoding unknown proteins. Phylogenetic and recombination analyses showed EKPV-NSW to be the distinct available candidate genome of chordopoxviruses.

show abstract

Section: Discussionmentioning

confidence: 99%

RETRACTED ARTICLE: Molecular and microscopic characterization of a novel Eastern grey kangaroopox virus genome directly from a clinical sample

Sarker

Roberts

Tidd

et al. 2017

Sci Rep

View full text Add to dashboard Cite

show abstract

“…OPXV species that encode a full-length CP77 ortholog (MPXV, TATV, AKMV, SKPV, and VPXV) can replicate in both the parental and ΔSAMD9L CHO cells, while OPXV species that have lost the CP77 gene (VACV, ECTV, and CMLV) can replicate only in ΔSAMD9L CHO cells. Interestingly, RNCV, which encodes a fusion protein that contains only the N-terminal 406 aa of the CP77 ortholog (47), can also replicate in CHO cells, albeit with reduced efficiency compared to that in ΔSAMD9L CHO cells. The RNCV genome is closely related to those of the other two North American OPXVs, with the largest difference being a 25-kbp deletion in the left terminal region of RCNV that removed 12 complete genes and created an in-frame gene fusion of the CP77 ortholog and the chemokine binding protein (47).…”

Section: Discussionmentioning

confidence: 99%

“…Interestingly, RNCV, which encodes a fusion protein that contains only the N-terminal 406 aa of the CP77 ortholog (47), can also replicate in CHO cells, albeit with reduced efficiency compared to that in ΔSAMD9L CHO cells. The RNCV genome is closely related to those of the other two North American OPXVs, with the largest difference being a 25-kbp deletion in the left terminal region of RCNV that removed 12 complete genes and created an in-frame gene fusion of the CP77 ortholog and the chemokine binding protein (47). The difference between the three North American OPXVs in terms of their replication in CHO cells correlates with our observation that the N-terminal seven ankyrin repeats were less effective than the full-length CP77 in inhibiting chSAMD9L.…”

Section: Discussionmentioning

confidence: 99%

Identification of CP77 as the Third Orthopoxvirus SAMD9 and SAMD9L Inhibitor with Unique Specificity for a Rodent SAMD9L

Zhang

Meng

Townsend

et al. 2019

J Virol

View full text Add to dashboard Cite

Orthopoxviruses (OPXVs) have a broad host range in mammalian cells, but Chinese hamster ovary (CHO) cells are nonpermissive for vaccinia virus (VACV).Here, we revealed a species-specific difference in host restriction factor SAMD9L as the cause for the restriction and identified orthopoxvirus CP77 as a unique inhibitor capable of antagonizing Chinese hamster SAMD9L (chSAMD9L). Two known VACV inhibitors of SAMD9 and SAMD9L (SAMD9&L), K1 and C7, can bind human and mouse SAMD9&L, but neither can bind chSAMD9L. Clustered regularly interspaced short palindromic repeat (CRISPR)-Cas9 knockout of chSAMD9L from CHO cells removed the restriction for VACV, while ectopic expression of chSAMD9L imposed the restriction for VACV in a human cell line, demonstrating that chSAMD9L is a potent restriction factor for VACV. In contrast to K1 and C7, cowpox virus CP77 can bind chSAMD9L and rescue VACV replication in cells expressing chSAMD9L, indicating that CP77 is yet another SAMD9L inhibitor but has a unique specificity for chSAMD9L. Binding studies showed that the N-terminal 382 amino acids of CP77 were sufficient for binding chSAMD9L and that both K1 and CP77 target a common internal region of SAMD9L. Growth studies with nearly all OPXV species showed that the ability of OPXVs to antagonize chSAMD9L correlates with CP77 gene status and that a functional CP77 ortholog was maintained in many OPXVs, including monkeypox virus. Our data suggest that a species-specific difference in rodent SAMD9L poses a barrier for cross-species OPXV infection and that OPXVs have evolved three SAMD9&L inhibitors with different specificities to overcome this barrier. IMPORTANCE Several OPXV species, including monkeypox virus and cowpox virus, cause zoonotic infection in humans. They are believed to use wild rodents as the reservoir or intermediate hosts, but the host or viral factors that are important for OPXV host range in rodents are unknown. Here, we showed that the abortive replication of several OPXV species in a Chinese hamster cell line was caused by a species-specific difference in the host antiviral factor SAMD9L, suggesting that SAMD9L divergence in different rodent species poses a barrier for cross-species OPXV infection. While the Chinese hamster SAMD9L could not be inhibited by two previously identified OPXV inhibitors of human and mouse SAMD9&L, it can be inhibited by cowpox virus CP77, indicating that OPXVs encode three SAMD9&L inhibitors with different specificities. Our data suggest that OPXV host range in broad rodent species depends on three SAMD9&L inhibitors with different specificities. KEYWORDS host range, host restriction factor, poxvirus, vaccinia virus T he Orthopoxvirus (OPXV) genus of the Poxviridae family consists of more than 10 closely related species, including the human pathogen variola virus (VARV) (the causative agent for smallpox), the smallpox vaccine vaccinia virus (VACV), and the emerging Citation Zhang F, Meng X, Townsend MB, Satheshkumar PS, Xiang Y. 2019. Identification of CP77 as the third orthopoxvirus SAMD9...

show abstract

“…OPXV species that encode a full-length CP77 ortholog (MPXV, TATV, AKMV, SKPV and VPXV) can replicate in both the parental and ΔSAMD9L CHO cells, while OPXV species that have lost CP77 gene (VACV, ECTV, and CMLV) can only replicate in ΔSAMD9L CHO cells. Interestingly, RNCV, which encodes a fusion protein that contains only the N-terminal 406 aa of CP77 ortholog (48), can also replicate in CHO cells, albeit with reduced efficiency compared to that in ΔSAMD9L CHO cells. The RNCV genome is closely related to that of the other two North American OPXVs, with the largest difference a 25 kbp deletion in the left terminal region of RCNV that removed 12 complete genes and created an in-frame gene fusion of CP77 ortholog and the chemokine binding protein (48).…”

Section: Discussionmentioning

confidence: 99%

“…Interestingly, RNCV, which encodes a fusion protein that contains only the N-terminal 406 aa of CP77 ortholog (48), can also replicate in CHO cells, albeit with reduced efficiency compared to that in ΔSAMD9L CHO cells. The RNCV genome is closely related to that of the other two North American OPXVs, with the largest difference a 25 kbp deletion in the left terminal region of RCNV that removed 12 complete genes and created an in-frame gene fusion of CP77 ortholog and the chemokine binding protein (48). The difference between the three North American OPXVs in terms of their replication in CHO cells correlates with our observation that the N-terminal seven ankyrin repeats was less effective than the full-length CP77 in inhibiting chSAMD9L.…”

Section: Discussionmentioning

confidence: 99%

Identification of CP77 as the third orthopoxvirus SAMD9L inhibitor with a unique specificity for a rodent SAMD9L

Zhang

Meng

Townsend³

et al. 2019

Preprint

View full text Add to dashboard Cite

24 25 Orthopoxviruses (OPXVs) have a broad host range in mammalian cells, but 26 Chinese hamster ovary (CHO) cells are non-permissive for vaccinia virus (VACV). Here, 27 IMPORTANCE: 47 Several OPXV species, including monkeypox virus and cowpox virus, cause 48 zoonotic infection in humans. They are believed to use wild rodents as the reservoir or 49 intermediate hosts, but the host or viral factors that are important for OPXV host range in 50 rodents are unknown. Here, we showed that the abortive replication of several OPXV 51 species in a Chinese hamster cell line was caused by a species-specific difference in the 52 host antiviral factor SAMD9L, indicating that SAMD9L divergence in different rodent 53 species poses a barrier for cross-species OPXV infection. While the Chinese hamster 54 SAMD9L could not be inhibited by two previously identified OPXV inhibitors of human 55 and mouse SAMD9L, it can be inhibited by cowpox virus CP77, indicating that OPXVs 56 encode three SAMD9L inhibitors with different specificity. Our data suggest that OPXV 57 host range in broad rodent species depends on three SAMD9L inhibitors with different 58 specificities. 59 60 (VPXV) are recognized as the North American OPXVs for being endemic in North 70America (2). VARV has been eradicated from nature, but the cessation of smallpox 71 vaccination and the waning of anti-OPXV herd immunity have increased the risk of 72 zoonotic OPXV infections. MPXV is highly virulent in humans (3), and the recent 73 increase in human monkeypox cases across a wide geographic area is a concern for 74 global health security (4). CPXV and VACV are responsible for zoonoses in Europe, 75Asia and South America (5, 6). Novel OPXV species have also been discovered in recent 76 human cases (7, 8), including Akhmeta virus (AKMV) isolated from the town of 77 Akhmeta, Georgia (country). 78OPXVs vary greatly in their animal host range (2), with some, such as VARV, 79 CMLV and TATV, only known to infect a single mammalian species, while others, such 80 as MPXV, CPXV and VACV, capable of infecting a wide variety of mammalian hosts. 81

show abstract

The genomes of three North American orthopoxviruses

Cited by 15 publications

References 39 publications

RETRACTED ARTICLE: Molecular and microscopic characterization of a novel Eastern grey kangaroopox virus genome directly from a clinical sample

RETRACTED ARTICLE: Molecular and microscopic characterization of a novel Eastern grey kangaroopox virus genome directly from a clinical sample

Identification of CP77 as the Third Orthopoxvirus SAMD9 and SAMD9L Inhibitor with Unique Specificity for a Rodent SAMD9L

Identification of CP77 as the third orthopoxvirus SAMD9L inhibitor with a unique specificity for a rodent SAMD9L

Contact Info

Product

Resources

About