Short-lived infected cells support virus replication in sooty mangabeys naturally infected with simian immunodeficiency virus: implications for AIDS pathogenesis.
Sooty mangabeys (SMs) naturally infected with simian immunodeficiency virus (SIV) do not develop AIDS despite high levels of virus replication. At present, the mechanisms underlying this disease resistance are poorly understood. Here we tested the hypothesis that SIV-infected SMs avoid immunodeficiency as a result of virus replication occurring in infected cells that live significantly longer than human immunodeficiency virus (HIV)-infected human cells. To this end, we treated six SIV-infected SMs with potent antiretroviral therapy (ART) and longitudinally measured the decline in plasma viremia. We applied the same mathematical models used in HIV-infected individuals and observed that SMs naturally infected with SIV also present a two-phase decay of viremia following ART, with the bulk (92 to 99%) of virus replication sustained by short-lived cells (average life span, 1.06 days), and only 1 to 8% occurring in longer-lived cells. In addition, we observed that ART had a limited impact on CD4(+) T cells and the prevailing level of T-cell activation and proliferation in SIV-infected SMs. Collectively, these results suggest that in SIV-infected SMs, similar to HIV type 1-infected humans, short-lived activated CD4(+) T cells, rather than macrophages, are the main source of virus production. These findings indicate that a short in vivo life span of infected cells is a common feature of both pathogenic and nonpathogenic primate lentivirus infections and support a model for AIDS pathogenesis whereby the direct killing of infected cells by HIV is not the main determinant of disease progression.
Gordon
Shari N
SN
University of Pennsylvania School of Medicine, 705 Stellar-Chance Laboratories, 422 Curie Boulevard, Philadelphia, PA 19143, USA.
Dunham
Richard M
RM
Engram
Jessica C
JC
Estes
Jacob
J
Wang
Zichun
Z
Klatt
Nichole R
NR
Paiardini
Mirko
M
Pandrea
Ivona V
IV
Apetrei
Cristian
C
Sodora
Donald L
DL
Lee
Ha Youn
HY
Haase
Ashley T
AT
Miller
Michael D
MD
Kaur
Amitinder
A
Staprans
Silvija I
SI
Perelson
Alan S
AS
Feinberg
Mark B
MB
Silvestri
Guido
G
D000818:Animals; D019380:Anti-HIV Agents / Q000627:therapeutic use; D018791:CD4 Lymphocyte Count; D016665:Cercocebus atys / Q000821:virology*; D008962:Models, Theoretical; D015302:Simian Immunodeficiency Virus / Q000254:growth & development*; D019562:Viral Load; D014766:Viremia
D019380:Anti-HIV Agents