Overexpression of PTEN impairs the activation of endothelial nitric oxide synthase (eNOS) and the release of vascular endothelial growth factor (VEGF) . By upregulating PTEN, human CMV suppresses Akt-mediated eNOS activation . Endothelial nitric oxide synthase (eNOS) expression and activity are both early events in atherosclerosis. Inhibiting eNOS, which results in endothelial dysfunction, may be the mechanism through which HCMV causes atherosclerosis . Notably, HCMV's inhibitory effect on eNOS activation is mediated via up-regulation of PTEN and activation of the stress signal p38 MAPK . SARS-COV-2 can interfere with NO metabolism and signaling pathways to break the Blood-Brain/Testi barrier . Hantavirus E protein's PTEN system is equivalent to upregulating PTEN. It suppressed the activation of eNOS via the Akt signaling pathway, resulting in inadequate nitric oxide generation. It caused endothelial dysfunction in the vascular system.