Biology Reference
In-Depth Information
T A B L E
14.2. Cytokine Regulation of the HIV Life Cycle
Induction
Suppression
Bifunctional Cytokines
IL-1, IL-3, IL-6, IL-7, IL-12,
IL-18, TNFs, CD30L,
M-CSF, GM-CSF
IFN-a/b,
IL-13, IL-16,
MDC*
IL-2, IL-4, IL-10, IFN-g,
TGF-b, MCP-1,
y
RANTES, MIP-1a, MIP-1b
z
* Monocyte-derived chemokine (MDC) has been described to suppress virus replication in activated
PBMC (Pal et al., 1997) and, recently, in MDM (Cota et al., 2000b).
y
Monocyte chemotactic protein 1 (MCP-1) has been associated with both inhibitory and enhancing
e¨ects in PBMC (Frade et al., 1997; Kinter et al., 1998; Vicenzi et al., 2000).
z
Although the CC chemokines RANTES, MIP1-a, and MIP1-b are potent suppressors of HIV
entry and replication in T lymphocytes (Cocchi et al., 1995), they have also shown inductive e¨ects
in both T cells and macrophages (Dolei et al., 1998; Kinter et al., 1998; Schmidtmayerova et al.,
1996).
Similarly, IL-3, IL-5, and granulocyte-macrophage colony-stimulating factor
(GM-CSF ) receptors are type I receptors that associates with a 150-kD trans-
membrane subunit endowed with WSXWS domains and transducing the cyto-
kine-mediated signal to the target cells (Taga and Kishimoto, 1992).
CYTOKINE SIGNALING AND INTERFERENCE WITH
HIV REPLICATION
Cytokines can enhance or inhibit virus expression from cells infected chroni-
cally with HIV. Enhancement of virus replication or expression is the dominant
e¨ect of several pro-in¯ammatory cytokines, such as TNFs and IL-1. In addi-
tion, several other cytokines have been described as inducers of virus replication
(Al-Harthi et al., 1998; Folks et al., 1987; Gendelman et al., 1988; Koyanagi et
al., 1988; Poli et al., 1990; Smithgall et al., 1996) ( Table 14.2). On the other
hand, only a restricted number of cytokines, namely IFNs (Shirazi and Pitha,
1992, 1993; Shirazi et al., 1994), IL-13 (Montaner et al., 1993, 1997), and IL-16
(Amiel et al., 1999; Baier and Kurth, 1997; Maciaszek et al., 1997; Truong et
al., 1999; Zhou et al., 1999) have shown clear-cut inhibitory e¨ects on virus
production. Finally, several cytokines can exert either enhancing or inhibitory
e¨ects on virus multiplication, depending from the cell type (T lymphocytes vs.
macrophages, or primary cells vs. cell lines) or the experimental conditions
(e.g., as a function of whether the cytokine was added before, at the same time,
or after infection) ( Koyanagi et al., 1988; Lazdins et al., 1991; Poli et al., 1991,
1992) (Table 14.2).
Several biological e¨ects caused by cell stimulation with TNF-a are medi-
ated by the activation of transcription factors, such as nuclear factor (NF )-kB
and AP1, which also play an important role in HIV expression. NF-kB(a
heterodimer typically composed of p50/p65 subunits) is normally present in the
