Effects of chloroquine and cytochalasin B on the infection of cells by Sindbis virus and vesicular stomatitis virus

Abstract

The effects of cytochalasin B and chloroquine on the process of endocytosis of Sindbis virus particles and polystyrene spheres were determined by electron microscopy. The effects of these agents on the process of infection (attachment, penetration, and uncoating) of BHK-21 cells by Sindbis virus and vesicular stomatitis virus were also determined. Cytochalasin B completely blocked ingestion of Sindbis virus particles or latex spheres by BHK cells but had no effect on the ability of Sindbis virus or vesicular stomatitis virus to infect or replicate in BHK cells. Chloroquine did not inhibit the ingestion of either latex spheres or virus particles but greatly reduced the yields of virus produced. These data suggest that endocytosis is not essential for the infection of cultured cells by Sindbis virus or vesicular stomatitis virus.

Innate antiviral defenses in body fluids and tissues

“…It was also determined that other simple inorganic amines can suppress plaque formation of herpes simplex type 1 virus, Semliki Forest virus, respiratory syncitial virus, rhinovirus 13, and influenza A virus. Similar results have been reported for ammonium chloride and other lysomotropic amines by other investigators (Jensen et al, 1961;Banfield and Kisch, 1973;Norkin and Einck, 1978;Helenius et al, 1980;Coombs et al, 1981). Although ammonium ions significantly inhibit several types of viruses, their breadth of antiviral activity is somewhat less than the inhibitors found in the plasma, gastrointestinal tract, and nervous system, as described later.…”

Virus Entry into Animal Cells

“…Since the mode of acid-activated, endocytosis-dependent entry of alphaviruses presented here is not unanimously accepted, it may be important to discuss some of the objections that have been raised. Because infection by Sindbis virus is not inhibited by cytochalasin B, Coombs et al (1981) concluded that endocytosis is not essential for infection. However, it is known that, while this microfilament inhibitor blocks phagocytosis, it leaves coated vesicle-mediated pinocytic processes essentially unaffected (Steinman et al, 1983).…”

Of chloroquine and COVID-19

“…The case of chikungunya virus (CHIKV) is of specific interest: chloroquine showed promising antiviral activity in vitro (Coombs et al, 1981;Delogu and de Lamballerie, 2011), but was shown to enhance alphavirus replication in various animal models (Maheshwari et al, 1991;Roques et al, 2018;Seth et al, 1999), most probably because of the immune modulation and anti-inflammatory properties of chloroquine in vivo (Connolly et al, 1988;Katz and Russell, 2011;Savarino et al, 2003). In a nonhuman primate model of CHIKV infection, chloroquine treatment was shown to exacerbate acute fever and delay the cellular immune response, leading to an incomplete viral clearance (Roques et al, 2018).…”