Reprints
PubMed
CAVEAT LECTOR
A SKEPTICAL LOOK AT VIRAL IMMUNE EVASION
Ila A. Davis and BarryT. Rouse.
Department of Microbiology, University of Tennessee, Knoxville, Tennessee, 37996
Received 11/25/ 97 Accepted 11/28/97
2. INTRODUCTION
The raison d'être of the adaptive immune system has been a topic of discourse amongst biologists. Some suggested the system evolved to preserve tissue integrity and eliminate cancer (1) but others might advocate that the driving force was the need by long-lived animals to control invasion and residence by agents which can rapidly evolve ways to bypass the innate defenses. The adaptive immune system, as we see it today (in mammals such as ourselves) successfully defends the body against all but a few microbes. We know that the absence or malfunction of certain components of adaptive immune defenses widens the spectrum of agents which can cause disease. As such, agents which are successful invaders and achieve residence may teach us valuable lessons on how the immune system itself functions (2). In addition, a careful analysis of a microbe's properties may reveal tactics which permit them to deal with host immunity, a strategy known as "immune evasion". So far, most such strategies have been identified only by in vitro analysis and few have been shown to act similarly within the body of their natural hosts.
Prominent among agents which succeed in establishing stable long-term relationships with their hosts are herpes viruses (HV). Humans can be infected with at least eight such viruses. Some HV achieve persistence, existing in a latent state, in 80% or more of the population and have minimal consequences in immune competent individuals. HV have numerous candidate evasion mechanisms and have been favorite subjects of study by many investigators. Table 1 lists some of the better studied immune evasion strategies of herpes as well as other viral pathogens.
Table 1: Selected Methods of Viral Evasion
|
VIRUS |
GENE/gene product |
EVASION MECHANISM |
REFERENCE
|
|
Human cytomegalovirus |
UL-18 |
Resist NK cell killing |
6 |
|
Murine cytomegalovirus |
M144 |
Resist NK cell killing |
7 |
|
Myxoma |
MT-7 |
IFN-g Receptor homologue |
13 |
|
Vaccinia |
B18R |
IFN Receptor homologue |
11 |
|
Vaccinia |
E3, K3 |
Interfere with IFN induced intracellular signalling |
10 |
|
Myxoma |
T2 |
TNFRII (p75) homologue |
9 |
|
Cowpox |
crmB, crmC |
TNFRII (p75) homologue |
9 |
|
Cowpox |
CrmA |
Inhibitor of IL-1b converting enzyme |
12 |
|
Herpes simplex virus |
gC-1 |
Inhibit complement function |
17, 18 |
|
Herpes virus saimiri |
CCPH |
Inhibit complement function |
15 |
|
Herpes virus saimiri |
HVS-A15 |
Inhibit complement membrane attack complex |
16 |
|
Adenovirus |
E3-19K |
Interfere with MHC I antigen presentation |
35 |
|
Herpes simplex virus |
ICP47 |
Interfere with MHC I antigen processing |
24 |
|
Human cytomegalovirus |
US2, US11, US6, US3 |
Interfere with MHC I antigen processing |
25, 26, 27, 28 |
|
Murine cytomegalovirus |
M152/gp40 |
Interfere with MHC I antigen processing |
29 |
|
Human immunodeficiency virus |
nef |
Interfere with MHC I antigen presentation |
38 |
|
Epstein-Barr virus |
EBNA1 |
Interfere with MHC I antigen presentation |
31 |
|
Murine cytomegalovirus |
M04/gp34 |
Alter surface expression of MHC I |
30 |
|
Adenovirus |
E1B-55K, E4orf6 |
Protection against apoptosis via p53 inactivation |
42 |
|
Adenovirus |
E1B-19K, E3-14.7K, E310.4K/14.5K |
Protect against TNF induced apoptosis |
43 |
|
Equineherpes virus-2 |
E8 |
Protect against death receptor induced apoptosis |
44 |
|
Herpesvirus saimiri |
ORF71 |
Protect against death receptor induced apoptosis |
44 |
|
Molluscum contagiosum virus |
ORF159L |
Protect against death receptor induced apoptosis |
44 |
|
Bovine herpesvirus-4, Human herpes virus-8 |
unidentified |
Protect against death receptor induced apoptosis |
44 |
|
Epstein-Barr virus |
LMP1, BHRF1 |
Protection against apoptosis via bcl-2 upregulation and homology |
46, 47 |
|
Epstein-Barr virus |
EBNA-5, BZLF1 |
Protection against p53 induced apoptosis |
48, 49 |
|
Herpes simplex virus-1 |
g34.5, ICP4 |
Protection against apoptosis |
50 |
|
Epstein-Barr virus |
BZLF2 |
Prevention of surface expression of MHC II |
56 |
|
Herpes simplex virus |
US7, US8 |
Fc receptor homologues: prevent complement neutralization and ADCC |
65 |
In this brief review, we outline some of the more prominent mechanisms representing immune evasion as measured in vitro and comment as to whether such putative evasion measures actually function similarly in vivo. Our objective is to evaluate if immune evasion in the complex environment of the body actually occurs or whether these tactics are misleading in vitro phenomena.