Table 1. Open in new tab Positively...

Gene

OPG

Sites^a

Features and function

References

A37R

OPG163

V46A/I

A deletion mutant is highly attenuated in the intranasal and intraperitoneal mouse challenge models; inhibits MHC Class II-restricted antigen presentation

Rehm et al. (2010); Roper (2006)

A43R

OPG172

A126V

Putative Type I membrane protein; a deletion mutant produces significantly smaller lesions than the control in the skin of mice

Sood and Moss (2010)

B4R

OPG188

V265I
S419R

Poxin; cleaves 2′3′ cGAMP to restrict STING-dependent signaling

Eaglesham et al. (2019)

B5R

OPG189

K185 R
R506H/C

ANK repeat- and PRANC domain-containing protein; an ectromelia virus deletion mutant showed decreased spread to organs and was attenuated during mouse infection

Burles et al. (2014)

B8R

OPG192

G100E

Endoplasmic reticulum resident protein; a deletion mutant is attenuated in a murine intradermal model (smaller lesions than the control virus)

Price et al. (2000)

B13 R

OPG200

D52G
E134G

Cytosolic virulence factor; inhibits IκB kinase

Chen, Jacobs, and Smith (2006); Chen et al. (2008)

B20R

OPG209

I11V
L21F

TNF receptor

Chen et al. (2005)

B21R

OPG210

A98D
V173I
N334I
E1862D

Inhibits TCR-mediated stimulation; deletion reduces virulence in a non-human primate model

Alzhanova et al. (2014)

C6R

OPG044

T109A

Virulence factor that inhibits DDX3

Schröder, Baran, and Bowie (2008)

D13 L

OPG031

T80M
C241Y

Inactivates DNA sensing and enhances virulence by binding Ku

Rivera-Calzada et al. (2022)

F3L

OPG065

A17T
H61N

Competes with ZBP1 for Z-DNA binding; blocks necroptosis

Koehler et al. (2021)

G7R

OPG091

V62I
S73N

Enzyme activity; deletion, or catalytically inactive mutants cause less severe disease in mice than WT viruses

Senkevich et al. (2008)

J3L/J1R^b

OPG003

A188V
D488N

ANK repeat and F-box containing protein; targets RIPK3 for degradation and inhibits necroptosis

Liu et al. (2021)

N3R

OPG016

E80V

Secreted protein; functions as a competitive antagonist of the NKG2D activating receptor

Campbell et al. (2007)

O1L

OPG037

C144Y

ANK repeat containing protein; prevents apoptotic functions of the apoptosome

Ryerson et al. (2017)

Table 1.

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Positively selected genes with a role in immunomodulation and/or virulence.

Gene	OPG	Sites^a	Features and function	References
A37R	OPG163	V46A/I	A deletion mutant is highly attenuated in the intranasal and intraperitoneal mouse challenge models; inhibits MHC Class II-restricted antigen presentation	Rehm et al. (2010); Roper (2006)
A43R	OPG172	A126V	Putative Type I membrane protein; a deletion mutant produces significantly smaller lesions than the control in the skin of mice	Sood and Moss (2010)
B4R	OPG188	V265I S419R	Poxin; cleaves 2′3′ cGAMP to restrict STING-dependent signaling	Eaglesham et al. (2019)
B5R	OPG189	K185 R R506H/C	ANK repeat- and PRANC domain-containing protein; an ectromelia virus deletion mutant showed decreased spread to organs and was attenuated during mouse infection	Burles et al. (2014)
B8R	OPG192	G100E	Endoplasmic reticulum resident protein; a deletion mutant is attenuated in a murine intradermal model (smaller lesions than the control virus)	Price et al. (2000)
B13 R	OPG200	D52G E134G	Cytosolic virulence factor; inhibits IκB kinase	Chen, Jacobs, and Smith (2006); Chen et al. (2008)
B20R	OPG209	I11V L21F	TNF receptor	Chen et al. (2005)
B21R	OPG210	A98D V173I N334I E1862D	Inhibits TCR-mediated stimulation; deletion reduces virulence in a non-human primate model	Alzhanova et al. (2014)
C6R	OPG044	T109A	Virulence factor that inhibits DDX3	Schröder, Baran, and Bowie (2008)
D13 L	OPG031	T80M C241Y	Inactivates DNA sensing and enhances virulence by binding Ku	Rivera-Calzada et al. (2022)
F3L	OPG065	A17T H61N	Competes with ZBP1 for Z-DNA binding; blocks necroptosis	Koehler et al. (2021)
G7R	OPG091	V62I S73N	Enzyme activity; deletion, or catalytically inactive mutants cause less severe disease in mice than WT viruses	Senkevich et al. (2008)
J3L/J1R^b	OPG003	A188V D488N	ANK repeat and F-box containing protein; targets RIPK3 for degradation and inhibits necroptosis	Liu et al. (2021)
N3R	OPG016	E80V	Secreted protein; functions as a competitive antagonist of the NKG2D activating receptor	Campbell et al. (2007)
O1L	OPG037	C144Y	ANK repeat containing protein; prevents apoptotic functions of the apoptosome	Ryerson et al. (2017)

Gene	OPG	Sites^a	Features and function	References
A37R	OPG163	V46A/I	A deletion mutant is highly attenuated in the intranasal and intraperitoneal mouse challenge models; inhibits MHC Class II-restricted antigen presentation	Rehm et al. (2010); Roper (2006)
A43R	OPG172	A126V	Putative Type I membrane protein; a deletion mutant produces significantly smaller lesions than the control in the skin of mice	Sood and Moss (2010)
B4R	OPG188	V265I S419R	Poxin; cleaves 2′3′ cGAMP to restrict STING-dependent signaling	Eaglesham et al. (2019)
B5R	OPG189	K185 R R506H/C	ANK repeat- and PRANC domain-containing protein; an ectromelia virus deletion mutant showed decreased spread to organs and was attenuated during mouse infection	Burles et al. (2014)
B8R	OPG192	G100E	Endoplasmic reticulum resident protein; a deletion mutant is attenuated in a murine intradermal model (smaller lesions than the control virus)	Price et al. (2000)
B13 R	OPG200	D52G E134G	Cytosolic virulence factor; inhibits IκB kinase	Chen, Jacobs, and Smith (2006); Chen et al. (2008)
B20R	OPG209	I11V L21F	TNF receptor	Chen et al. (2005)
B21R	OPG210	A98D V173I N334I E1862D	Inhibits TCR-mediated stimulation; deletion reduces virulence in a non-human primate model	Alzhanova et al. (2014)
C6R	OPG044	T109A	Virulence factor that inhibits DDX3	Schröder, Baran, and Bowie (2008)
D13 L	OPG031	T80M C241Y	Inactivates DNA sensing and enhances virulence by binding Ku	Rivera-Calzada et al. (2022)
F3L	OPG065	A17T H61N	Competes with ZBP1 for Z-DNA binding; blocks necroptosis	Koehler et al. (2021)
G7R	OPG091	V62I S73N	Enzyme activity; deletion, or catalytically inactive mutants cause less severe disease in mice than WT viruses	Senkevich et al. (2008)
J3L/J1R^b	OPG003	A188V D488N	ANK repeat and F-box containing protein; targets RIPK3 for degradation and inhibits necroptosis	Liu et al. (2021)
N3R	OPG016	E80V	Secreted protein; functions as a competitive antagonist of the NKG2D activating receptor	Campbell et al. (2007)
O1L	OPG037	C144Y	ANK repeat containing protein; prevents apoptotic functions of the apoptosome	Ryerson et al. (2017)

Notes: ^aAmino acid positions refer to MPXV NC_003310 (Zaire-96-I-16).

Paralog genes located in the ITR.

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