Statins Could Be Used to Control Replication of Some Viruses, Including HIV-1

Abstract

Statins are mainly known for their plasma cholesterol-lowering properties and are widely used for the prevention of cardiovascular diseases. They however also exert pleiotropic effects through a variety of mechanisms, among which several immunosuppressive effects that are unrelated to their cholesterol-lowering activity. Interestingly, there has been recent evidence of antiviral effects, including preliminary studies on the efficacy of statins against HIV-1. This paper more particularly focuses on the specific inhibition of the binding of leukocyte function-associated antigen-1 (LFA-1) to intercellular adhesion molecule (ICAM-1) by statins, independently of the inhibition of HMGCoA reductase. Targeting the statin-binding site within LFA-1 or regulating LFA-1 affinity by inhibiting prenylation of the small GTPases could prove useful to treat inflammatory, autoimmune diseases and possibly viral infections, including HIV-1.

Efficiency of Human Immunodeficiency Virus Type 1 Postentry Infection Processes: Evidence against Disproportionate Numbers of Defective Virions

“…It is important to note that the properties of our transfection-generated virus may be different from those of virus in the host, which should contain cellular proteins obtained from the cells from which it was derived (13,21). The presence of these cellular proteins may increase infectivity.…”

Lipid Involvement in Viral Infections: Present and Future Perspectives for the Design of Antiviral Strategies

“…Impairment of cholesterol biosynthetic pathway by inhibitors of 3-hydroxy-3-methyl-glutaryl-CoaA reductase (3-HMG-CoA reductase) like statins, commonly used in treatment of cardiovascular disease, constitutes a novel antiviral approach [174,175,183]. The clinical success of these inhibitors for human disorders also indicates that inhibitors of lipid metabolism can be safe and effective for human therapy.…”

“…An additional effect of the treatment with statins, unrelated to the inhibition of 3-HMG-CoA reductase, is the inhibition of the binding of leukocyte function-associated antigen-1 (LFA-1) to the intercellular adhesion molecule (ICAM-1) [184], thus being immunomodulators and anti-inflammatory agents [185,186]. These properties can carry additional advantages for fighting HIV [174][175][176].…”

Statins as Antiviral and Anti-inflammatory Therapy in HIV Infection

“…Statin compounds exhibit anti-inflammatory and antiviral effects in vitro [5,[9][10][11][12]. Statins have been found in some, but not all, studies to inhibit HIV replication in vitro through an unclear mechanism [8,11,13,14].…”

“…In vitro models suggest that virions derived from cholesterol-depleted cells demonstrate reduced infectivity in vitro [9], and disruption of lipid rafts with cholesterol-depleting agents, such as statins, reduces HIV-1 particle production [9]. In addition, statins have demonstrated effects on protein prenylation and inhibit lymphocyte function antigen-1 (LFA-1) and intercellular adhesion molecule-1 (ICAM-1) interactions that influence viral entry and exit [9][10][11][12]15]. Conversely, statins may perturb the activation of immune cells and increase HIV transcription [10].…”