Virally induced CD4+ T cell depletion is not sufficient to induce AIDS in a natural host.
Peripheral blood CD4+ T cell counts are a key measure for assessing disease progression and need for antiretroviral therapy in HIV-infected patients. More recently, studies have demonstrated a dramatic depletion of mucosal CD4+ T cells during acute infection that is maintained during chronic pathogenic HIV as well as SIV infection. A different clinical disease course is observed during the infection of natural hosts of SIV infection, such as sooty mangabeys (Cercocebus atys), which typically do not progress to AIDS. Previous studies have determined that SIV+ mangabeys generally maintain healthy levels of CD4+ T cells despite having viral replication comparable to HIV-infected patients. In this study, we identify the emergence of a multitropic (R5/X4/R8-using) SIV infection after 43 or 71 wk postinfection in two mangabeys that is associated with an extreme, persistent (>5.5 years), and generalized loss of CD4+ T cells (5-80 cells/microl of blood) in the absence of clinical signs of AIDS. This study demonstrates that generalized CD4+ T cell depletion from the blood and mucosal tissues is not sufficient to induce AIDS in this natural host species. Rather, AIDS pathogenesis appears to be the cumulative result of multiple aberrant immunologic parameters that include CD4+ T cell depletion, generalized immune activation, and depletion/dysfunction of non-CD4+ T cells. Therefore, these data provide a rationale for investigating multifaceted therapeutic strategies to prevent progression to AIDS, even following dramatic CD4 depletion, such that HIV+ humans can survive normal life spans analogous to what occurs naturally in SIV+ mangabeys.
Milush
Jeffrey M
JM
University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
Reeves
Jacqueline D
JD
Gordon
Shari N
SN
Zhou
Dejiang
D
Muthukumar
Alagar
A
Kosub
David A
DA
Chacko
Elizabeth
E
Giavedoni
Luis D
LD
Ibegbu
Chris C
CC
Cole
Kelly S
KS
Miamidian
John L
JL
Paiardini
Mirko
M
Barry
Ashley P
AP
Staprans
Silvija I
SI
Silvestri
Guido
G
Sodora
Donald L
DL
D000163:Acquired Immunodeficiency Syndrome / Q000276:immunology*; D000595:Amino Acid Sequence; D000818:Animals; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology*; D016665:Cercocebus atys; D004195:Disease Models, Animal; D007108:Immune Tolerance; D008969:Molecular Sequence Data; D016097:Simian Acquired Immunodeficiency Syndrome / Q000276:immunology; D015302:Simian Immunodeficiency Virus