(A) Nonpathogenic SIV infections in SMs and AGMs are characterized by sustained CD4⁺ T cell counts and controlled viremia (viral load [VL]). There is early upregulation of transcripts for viral restriction factors (blue), of genes associated with dampening of T cell activation (pink), of antimicrobial defensins (red), and of ISGs (green). However, the expression of ISGs resolves rapidly, possibly due to upregulation of suppressors of the IFN response (yellow). Transcripts for the immune-dampening genes TGFB and IL10 are upregulated in chronic infection (pink). Myxovirus influenza virus resistance protein 1 (MX1) and IP10 are antiviral factors. Melanoma differentiation–associated protein 5 (MDA5) and retinoic acid–inducible gene I (RIG-I) are intracellular sensors of RNA viruses. IRF7, IFN regulatory factor 7. (B) In contrast, SIV infection of RMs is characterized by eventual loss of CD4⁺ T cells and corresponding loss of control of viremia. RMs have chronic expression of ISGs, accompanied by enhanced expression of proapoptotic factors (purple), as well as markers of T cell activation and exhaustion and of inflammation (pink). Antiviral host restriction factors: apolipoprotein B mRNA–editing enzyme, catalytic polypeptide–like 3 (APOBEC3), T cell receptor–interacting molecule (TRIM) family members. T cell–associated inhibitory factors: LAG3, IL10, programmed cell death ligand 1 (PDL1), soluble galactoside-binding lectin 3 (LGALS3; also known as galectin-3, a proapoptotic ISG), and IDO. Suppressors of IFN: adenosine deaminase, RNA-specific (ADAR), laboratory of genetics and physiology 2 (LGP2), and IFN-stimulated gene 15 (ISG15). Proapoptotic molecules: TRAIL and B cell CLL/lymphoma 2-like 14 (BCL2L14). Markers of T cell activation and exhaustion: MKI67 (marker of proliferation), CD38, CCR5, CXCL9, and CXCL11, TIM3, IL7-receptor (IL7R), and LAG3.