Preexisting infection with human T-cell lymphotropic virus type 2 neither exacerbates nor attenuates simian immunodeficiency virus SIVmac251 infection in macaques.
Coinfection with human T-cell lymphotropic virus type 2 (HTLV-2) and human immunodeficiency virus type 1 (HIV-1) has been reported to have either a slowed disease course or to have no effect on progression to AIDS. In this study, we generated a coinfection animal model and investigated whether HTLV-2 could persistently infect macaques, induce a T-cell response, and impact simian immunodeficiency virus SIV(mac251)-induced disease. We found that inoculation of irradiated HTLV-2-infected T cells into Indian rhesus macaques elicited humoral and T-cell responses to HTLV-2 antigens at both systemic and mucosal sites. Low levels of HTLV-2 provirus DNA were detected in the blood, lymphoid tissues, and gastrointestinal tracts of infected animals. Exposure of HTLV-2-infected or naïve macaques to SIV(mac251) demonstrated comparable levels of SIV(mac251) viral replication, similar rates of mucosal and peripheral CD4(+) T-cell loss, and increased T-cell proliferation. Additionally, neither the magnitude nor the functional capacity of the SIV-specific T-cell-mediated immune response was different in HTLV-2/SIV(mac251) coinfected animals versus SIV(mac251) singly infected controls. Thus, HTLV-2 targets mucosal sites, persists, and importantly does not exacerbate SIV(mac251) infection. These data provide the impetus for the development of an attenuated HTLV-2-based vectored vaccine for HIV-1; this approach could elicit persistent mucosal immunity that may prevent HIV-1/SIV(mac251) infection.
Gordon
Shari N
SN
Animal Models and Retroviral Vaccines Section, National Cancer Institute, NIH,Bethesda, Maryland 20892, USA.
Weissman
Anna R
AR
Cecchinato
Valentina
V
Fenizia
Claudio
C
Ma
Zhong-Min
ZM
Lee
Tzong-Hae
TH
Zaffiri
Lorenzo
L
Andresen
Vibeke
V
Parks
Robyn Washington
RW
Jones
Kathryn S
KS
Heraud
Jean Michel
JM
Ferrari
Maria Grazia
MG
Chung
Hye Kyung
HK
Venzon
David
D
Mahieux
Renaud
R
Murphy
Edward L
EL
Jacobson
Steven
S
Miller
Christopher J
CJ
Ruscetti
Francis W
FW
Franchini
Genoveffa
G
D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000821:virology; D003713:Dendritic Cells / Q000276:immunology / Q000821:virology; D016679:Genome, Viral; D015658:HIV Infections / Q000276:immunology; D015497:HIV-1 / Q000276:immunology; D015491:HTLV-II Infections / Q000276:immunology*; D015367:Human T-lymphotropic virus 2 / Q000276:immunology*; D006801:Humans; D007109:Immunity / Q000276:immunology; D007413:Intestinal Mucosa / Q000276:immunology / Q000821:virology; D008213:Lymphocyte Activation / Q000276:immunology; D008221:Lymphoid Tissue / Q000276:immunology / Q000821:virology; D008253:Macaca mulatta / Q000821:virology*; D015302:Simian Immunodeficiency Virus / Q000276:immunology*; D019562:Viral Load