Immunology 101 at poxvirus U: Immune evasion genes

doi:10.1006/smim.2000.0296

Seminars in Immunology

Volume 13, Issue 1, February 2001, Pages 59-66

https://doi.org/10.1006/smim.2000.0296 Get rights and content

Abstract

Poxviruses, unlike some other large DNA viruses, do not undergo a latent stage but rely on the expression of viral proteins to evade host immune responses. Of the many poxviral evasion genes identified, most target cytokines or other innate immune defenses. Resistance to interferons appears to be a priority as there are viral proteins that prevent their induction, receptor binding, and action. Additional poxviral proteins inhibit complement activation, chemokines, IL-1β and tumor necrosis factor. The identification of viral immune evasion genes and the determination of their roles in virus survival and spread contribute to our understanding of immunology and microbiology.

References (81)

CA Smith et al.
T2 open reading frame from the Shope Fibroma virus encodes a soluble form of the TNF receptor
Biochem Biophys Res Commun
(1991)
C Upton et al.
Myxoma virus expresses a secreted protein with homology to the tumor necrosis factor receptor gene family that contributes to viral virulence
Virology
(1991)
RF Massung et al.
Analysis of the complete genome of smallpox variola major virus strain Bangladesh-1975
Virology
(1994)
C Cameron et al.
The complete DNA sequence of myxoma virus
Virology
(1999)
DO Willer et al.
The complete genome sequence of Shope (rabbit) fibroma virus
Virology
(1999)
S Tomlinson
Complement defense mechanisms
Curr Opin Immunol
(1993)
CG Miller et al.
The cowpox virus-encoded homolog of the vaccinia virus complement control protein is an inflammatory modulatory protein
Virolgy
(1997)
M Engelstad et al.
A constitutively expressed vaccinia gene encodes a 42-kDa glycoprotein related to complement control factors that forms part of the extracellular virus envelope
Virology
(1992)
CA Dinarello
IL-18: A TH1-inducing, proinflammatory cytokine and new member of the IL-1 family
J Allergy Clin Immunol
(1999)
M Tanaka-Kataoka et al.
In vivo antiviral effect of interleukin 18 in a mouse model of vaccinia virus infection
Cytokine
(1999)

D Novick et al.

Interleukin-18 binding protein: a novel modulator of the Th1 cytokine response

Immunity

(1999)

Y Xiang et al.

Identification of human and mouse homologs of the MC51L-53L-54L family of secreted glycoproteins encoded by the molluscum contagiosum poxvirus

Virology

(1999)

S Calderara et al.

Orthopoxvirus IL-18 binding proteins: affinities and antagonistic activities

Virology

(2001)

CA Ray et al.

Viral inhibition of inflammation - cowpox virus encodes an inhibitor of the interleukin-1 β converting enzyme

Cell

(1992)

K Mossman et al.

Species specificity of ectromelia virus and vaccinia virus interferon-gamma binding proteins

Virology

(1995)

K Mossman et al.

Myxoma virus M-T7, a secreted homolog of the interferon-g receptor, is a critical virulence factor for the development of myxomatosis in European rabbits

Virology

(1996)

K Essani et al.

Multiple anti-cytokine activities secreted from tanapox virus-infected cells

Microb Pathog

(1994)

JA Symons et al.

Vaccinia virus encodes a soluble type 1 interferon receptor of novel stucture and broad species specificity

Cell

(1995)

OR Colamonici et al.

Vaccinia virus B18R gene encodes a type I interferon-binding protein that blocks interferon alpha transmembrane signaling

J Biol Chem

(1995)

CE Samuel

Antiviral actions of interferon. Interferon-regulated cellular proteins and their surprisingly selective antiviral activities

Virology

(1991)

E Beattie et al.

Vaccinia virus encoded eIF-2a homolog abrogates the antiviral effect of interferon

Virology

(1991)

TG Senkevich et al.

The genome of molluscum contagiosum virus: analysis and comparison with other poxviruses

Virology

(1997)

KA Graham et al.

The T1/35kDa family of poxvirus-secreted proteins bind chemokines and modulate leukocyte influx into virus-infected tissues

Virology

(1997)

CA Smith

Poxvirus genomes encode a secreted, soluble protein that preferentially inhibits β chemokine activity yet lacks sequence homology to known chemokine receptors

Virology

(1997)

L Martinez-Pomares et al.

Mapping and investigation of the role in pathogenesis of the major unique secreted protein of rabbitpox virus

Virology

(1995)

RF Massung et al.

DNA sequence analysis of conserved and unique regions of swinepox virus: identification of genetic elements supporting phenotypic observations including a novel G protein-coupled receptor homologue

Virology

(1993)

JX Cao et al.

Sequence analysis of HindIII Q2 fragment of capripoxvirus reveals a putative gene encoding a G-protein-coupled chemokine receptor homologue

Virology

(1995)

F-Q Hu et al.

Cowpox virus contains two copies of an early gene encoding a soluble secreted form of the type II TNF receptor

Virology

(1994)

CA Smith et al.

Cowpox virus genome encodes a second soluble homologue of cellular TNF receptors, distinct from CrmB, that binds TNF but not LT alpha

Virology

(1996)

SN Shchelkunov et al.

The genomic sequence analysis of the left and right species- specific terminal region of a cowpox virus strain reveals unique sequences and a cluster of intact ORFs for immunomodulatory and host range proteins

Virology

(1998)

N Chen et al.

Analysis of host response modifier ORFs of ectromelia virus, the causative agent of mousepox

Virus Res

(2000)

ST Howard et al.

Vaccinia virus homologues of the Shope fibroma virus inverted terminal repeat proteins and a discontinuous ORF related to the tumor necrosis factor receptor family

Virology

(1991)

M Schreiber et al.

Myxoma virus T2 protein, a tumor necrosis factor (TNF) receptor homolog, is secreted as a monomer and dimer that each bind rabbit TNFalpha, but the dimer is a more potent TNF inhibitor

J Biol Chem

(1996)

JL Macen et al.

Expression of the myxoma virus tumor necrosis factor receptor homologue and M11L genes is required to prevent virus-induced apoptosis in infected rabbit T lymphocytes

Virology

(1996)

CA Dinarello

Biologic basis for interleukin-1 in disease

Blood

(1996)

M Tewari et al.

Fas- and tumor necrosis factor-induced apoptosis is inhibited by the poxvirus crmA gene product

J Biol Chem

(1995)

A Alcami et al.

A soluble receptor for interleukin-1b encoded by vaccinia virus - a novel mechanism of virus modulation of the host response to infection

Cell

(1992)

MK Spriggs et al.

Vaccinia and cowpox viruses encode a novel secreted Interleukin-1-Binding protein

Cell

(1992)

TG Senkevich et al.

Domain structure, intracellular trafficking, and beta 2-microglobulin binding of a major histocompatibility complex class I homolog encoded by molluscum contagiosum virus

Virology

(1998)

GJ Kotwal et al.

Vaccinia virus encodes a secretory polypeptide structurally related to complement control proteins

Nature

(1988)

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¹: Corresponding author. Email: [email protected]

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