AIDS RESEARCH AND HUMAN RETROVIRUSES Volume 6, Number 12, 1990 Mary Ann Liebert, Inc., Publishers

Letter to the Editor

Extensive

Antigenic Mimicry by Retrovirus Capsid Proteins

Sir, Several retroviral proteins share amino acid sequence similarities with cellular proteins that are recognized as autoantigens in autoimmune diseases. '~4 Examples of antigenic mimicry by the major retroviral capsid protein (CA) include: (1) a region of SS-B (LA), a small nuclear ribonucleoprotein (snRNP) (Fig. 1 A), (2) a shared region of topoisomerase I and the acetylcholine and (3) a region of the 70 kD protein, receptor (ACR) (Fig. IB), '~3 These similarities to autoantigens another snRNP (Fig. 1C). are also present in CA of human immunodeficiency virus (HIV), and are modestly conserved among retroviruses (Fig. 1). I write to point out that recent evidence by Marcus-Sekura and co-workers suggests that regions in CA with similarities to autoantigens are frequently recognized by the humoral immune system.5 Epitope mapping studies revealed five different antigenic determinants of HIV CA, and suggested that these regions may be the immunodominant epitopes of CA.5 Three of the epitopes may be mapped precisely to regions of CA with similarity to the 70 kD snRNP. topoisomerase I and ACR, and SS-B (Fig. 2). I also identified a region of another autoantigen designated Sm, which is similar to one of the other CA determinants identified by epitope mapping (Fig. ID).4 Thus, four of five immunodominant epitopes of CA share amino acid sequence similarities to known autoantigens. I also wish to direct attention to the molecular model of CA proposed by Argos.6 He observed that the predicted secondary structure of CA shares with the coat proteins of picornaviruses a propensity to form multiple ß strands, and constructed a model of CA based on the known three-dimensional structure of the picomavirus coat proteins. This model predicts that the immunodominant epitopes of CA with sequence similarities to autoantigens are in exposed regions outside of the eight-stranded ß-barrel core of the protein, and are therefore potentially more accessible to the immune system (Fig. 2). Further evidence that this model of CA may have useful predictive value is provided by data that identify similarly exposed epitopes frequently recognized by primate cytotoxic T lymphocytes (CTL).7'8

Robert F. Garry and Immunology Department of Microbiology Tulane University School of Medicine New Orleans, LA 70112

SS-B HIV SIV FSV RSV

(La) I R

R I R Q V _Q R E G A Q

QTm

S P S K P L P E P F G P

P F G P G P S K L G p sir

B

Y N

Kj

pTIaTlInJm

Sm

HIV SIV FSV RSV

[p]r

h

p[â]n[gJqg RIS

FIG. 1. Comparison of retroviral major capsid protein (CA) and autoantigen amino acid sequences. CA sequences were aligned with the (A) SS-B (LA), (B) topoisomerase I (topo I) and acetylcholine receptor (ACR), and (C) 70 kD autoantigens as previously described. (D) CA is also aligned to the Sm (B /B) autoantigen.4'9 Conservative groups of amino acids indicated by shading were considered (K,R); (S,T,C); (P,G); (F,Y,W,H); (E,D,Q,N); and (A,I,V,L,M,F). HIV, human immunodeficiency virus; SIV, simian immunodeficiency virus; FSV, feline sarcoma virus; RSV, Rous sarcoma virus.

1361

1362

GARRY

SS-B

(La)

sequence

CTL

epitope

similarity

Sm sequence

Topoisomerase 1/

similarity

ACR sequence

similarity

70 Kd

CTL epitope

sequence

similarity

D

-*-

C-terminus

-*-

N-terminus

FIG. 2. Predicted structure of retroviral major capsid protein based on the known structure of picornavirus coat protein.6 The eight strands of the antiparallel ß-barrel core of CA are labelled B-I. The predicted exterior of the molecule is at the top and the interior is at the bottom. Sequences corresponding to immunoglobulin epitopes are grey,5 and sequences corresponding to cytotoxic T-lymphocyte epitopes are black.7-8 Regions of similarity to autoantigens are indicated.1_4

REFERENCES 1.

Query CC and Keene JD:

A human autoimmune protein associated with U1 RNA contains a region of homology that is cross-reactive with retroviral p30ea« antigen. Cell 1987;51:211-220. 2. Maul GG, Jimenez SA, Riggs E, and Ziemnicka-Zotula D: Determination of an epitope of the diffuse systemic sclerosis marker antigen DNA topoisomerase I: Sequence similarity with retroviral p30gag protein suggests a possible cause for autoimmunity in systemic sclerosis. Proc Nati Acad Sei (USA) 1989;86:8492-8496. 3. Kohsaka H, Yamamoto K, Fujii H, Miura H, Miyasaka N, Nishioka K, and Miyamoto T: Fine epitope mapping of the human SS-B/La protein: Identification of a distinct autoepitope homologous to a viral gag polyprotein. J Clin Invest 1990;85:1566-1574. 4. Talal N, Garry RF, Schur PH, Alexander SS, Dauphinee MJ, Livas JH, Ballester A, Takei M, and Dang H: A conserved idiotype and antibodies to retroviral proteins in systemic lupus erythematosus. J Clin Invest 1990;85:1866-1871.

Marcus-Sekura CJ, Warner AM, Zhang P-F, and Klutch M: Epitope mapping of the HIV-1 gag region by analysis of gag gene deletion fragments expressed in Escherichia coli defines eight antigenic determinants. AIDS Res Human Retroviruses 1990;6:317-327. Argos P. A possible homology between immunodeficiency virus p24 core protein and picornal viral coat protein: prediction of HIV p24 antigenic sites. EMBOJ 1989;8:779-785. Nixon DF, Townsend ARM, Elvin JG, Rizza CR, Gallwey J, and McMicheal AJ: HIV-1 gag-specific cytotoxic T lymphocytes defined with recombinant vaccinia virus and synthetic peptides. Nature

1988;336:484-487.

Yamamoto H, Miller MD, Tsubota H, Watkins DI, Mazzara GP, Stallard V, Panicali DL, Aldovini A, Young RA, and Letvin NL: Studies of cloned simian immunodeficiency virus-specific T lymphocytes: gag-specific cytotoxic T lymphocytes exhibit a restricted epitope specificity. J. Immunol. 1990;144:3385-3391. 9. Rokeach LA, Jannatipour M, Haselby JA, and Hoch SO: Primary structure of a human small nuclear ribonucleoprotein polyprotein as deduced by cDNA analysis. J Biol Chem 1990;264:5024-5030.