. 2008 May 30;4(5):e1000018. doi: 10.1371/journal.ppat.1000018

Table 1. Examples of Viruses and Viral Proteins Activating the Mitochondrial Pathway of Apoptosis.

Virus	Effector	Cellular Target	Effects	Reference
*Direct inducers of MMP*
AEV	2C	CEB and Cos-7 cells	Induction of the caspase cascade leading to apoptosis	[S154]
	VP3	Different cell lines	Induction of the caspase cascade leading to apoptosis	[S153]
BLV	G4	HeLa and yeast cells	Alterations of mitochondrial morphology; interacts with FPPS	[S140]
HBV	HBx	Hepatocytes VDAC	Δψ_m loss and MMP-dependent apoptosis	[S122–S124]
HCV	NS4A	Hepatocytes	Accumulation in mitochondria, Δψ_m loss, Cyt c release, casp-3 activation	[S155]
HIV-1	Vpr	CD4⁺ lymphocytes ANT/VDAC	Δψ_m loss, IMS proteins release, caspase cascade activation	[24;S41,S113,S115]
HTLV-1	p13(II)	Lymphocytes	Rapid flux of K+ and Ca²⁺ across IM, swelling, Δψ_m dissipation and fragmentation	[S135,S138]
HPV	E1̂E4	Keratinocytes	Displaces mitochondria from microtubules	[S152]
IAV	PB1-F2	Lung cells ANT3/VDAC1	Interaction with ANT3 and VDAC1	[S149]
PLV	Unknown	Neurons Bone marrow Lymphoid cells	JNK activation, Cyt c release, Δψ_m loss, Bax activation	[S176]
	2B 3A	Kidney cells	Perinuclear aggregation and ultrastructural alterations of mitochondria, Δψ_m loss	[S130]
WDSV	OrfC	Epithelial cells	Perinuclear clustering of mitochondria, Δψ_m loss, partial Cyt c release, signs of apoptosis	[S131,S132]
*Indirect MMP Facilitators*
ADV	E1A E4orf6	Epithelial cells	Inhibition of PP2A, PARP hyperactivation, AIF translocation; sensitization to TNFα and Fas; BH3-only protein expression	[41;S183,S187]
EBV	BALF1	Lymphoid cells	Antagonism of BHRF1(?)	[67]
FMDV	Unknown	Thyroid cells Kidney cells Dendritic cells	Reduction in the endogenous levels of Bcl-2, activation of caspases, release of Cyt c from mitochondria	[S206]
HCV	NS3	Hepatocytes	Casp-8-mediated apoptosis	[S171]
HIV-1	Env	CD4⁺ lymphocytes	Bax upregulation, Cyt c release, caspase activation; involvement of Cdk1, mTOR, p53 and NF-kB	[32,33;S160]
	Nef	Lymphocytes	Lysosomal membrane permeabilization, cathepsin D release, Bax activation, MMP-dependent cell death	[S158,S159]
	Protease	Lymphocytes Bcl-2/Casp-8	Bcl-2 depletion, NF-kB activation; Casp-8 activation, Bid cleavage, Cyt c release, Casp-9 and -3 activation, DFF and PARP cleavage	[36;S169]
	Tat	Neurons Tubulin	Accumulation at mitochondria, Δψ_m loss, ROS overproduction, caspase activation; degradation of MAP2; Bim activation; regulation of p53, Bax and Bcl-2	[34,35;S86,S161–S163,S165–S166]
HPV	E6	Epithelial cells	Sensitize cells to different apoptotic stimuli, via mechanisms that may depend or not on p53	[S191–S193]
	E7	Epithelial cells	Sensitization of cells to apoptosis induced by growth factor withdrawal, chemotherapeutic agents and UV rays	[S194–S196]
PLV	2Apro 3Cpro	HeLa cells	Caspase-dependent apoptosis	[S172,S173]
SARS-CoV	7a	Various cell lines	Inhibition of Bcl-X_L	[46]
VSV	M	Vero cells	Reduction of Bcl-X_L levels; caspase activation	[44;S199]
	P	Hamster cells	Unknown mechanism	[S203]
WNV	Capsid NS2B/NS3	Neurons	UPR, Bid and Bax translocation to mitochondria, Δψ_m dissipation, Cyt c release, caspase activation	[45;S207–S210]

Abbreviations: ADV, adenovirus; AEV, avian encephalomyelitis virus; AIF, apoptosis-inducing factor; ANT, adenine nucleotide translocase; BH3, Bcl-2 homology domain 3; BLV, bovine leukemia virus; Casp, caspase; Cdk1, cyclin-dependent kinase 1; CEB, chick embryo brain; Cyt c, cytochrome c; Δψ_m, mitochondrial transmembrane potential; DFF, DNA fragmentation factor; EBV, Epstein-Barr virus; Env, envelope glycoprotein complex; FMDV, foot-and-mouth disease virus; FPPS, farnesyl pyrophosphate synthetase; HBV, hepatitis B virus; HBx, HBV X protein, HCV, hepatitis C virus; HIV-1, human immunodeficiency virus 1; HPV, human papillomavirus; HTLV-1, human T lymphotropic virus 1; IAV, influenza A virus; IMS, mitochondrial intermembrane space; JNK, c-Jun N-terminal kinase; M, matrix protein; MAP2, microtubule-associated protein 2; MMP, mitochondrial membrane permeabilization; mTOR, mammalian target of rapamycin; NF-kB, nuclear factor-kappa B; NS; non structural protein; ORF, open reading frame; P, phosphoprotein P; PARP, poly(ADP-ribose) polymerase; PLV, poliovirus; PP2A, protein phosphatase 2A; ROS, reactive oxygen species; SARS-CoV; severe acute respiratory syndrome coronavirus; TNFα, tumor necrosis factor α; UPR, unfolded protein response; UV, ultraviolet; VDAC, voltage-dependent anion channel; Vpr, viral protein R; VSV, vesicular stomatitis virus; WDSV, Walleye dermal sarcoma virus; WNV, West Nile virus.