Innate antiviral defenses in body fluids and tissues

Abstract

Innate, non-specific, resistance mechanisms are important barriers to pathogens, particularly delaying virus multiplication at the onset of infections. These innate defense mechanisms include a series of mechanical barriers, pre-existing inhibitory molecules, and cellular responses with antimicrobial activity. The antiviral activities of these innate inhibitors reside in a variety of partly characterized substances. This review presents the innate antiviral inhibitors in cell cultures, urine, serum, the gastrointestinal tract, the nervous system, tissues of crustaceans, and saliva. Medical adaptation of the innate antiviral defense mechanisms may be useful for prevention and treatment of viral infections.

Fig. 1

Production of virus, interferon, and antibody during experimental infection of humans with influenza wild-type virus. Non-specific defenses include anatomic barriers, inhibitors, phagocytosis, fever, inflammation and IFN. Specific defenses include antibody and cell-mediated immunity. Data from a study by B. Murphy et al., National Institutes of Health (pers. commun.).

Fig. 2

Estimation of the molecular size of the UTIβ by size exclusion chromatography. Sera from different mammalian species were individually loaded onto a column (2.5×90 cm) of Sephacryl S-200. The column was equilibrated with phosphate buffered saline. Four-milliliter fractions were collected: the antiviral activity (depicted by the heavy line) in individual fractions was examined by the standard plaque reduction assay. The inset shows the calibration of the column. Reprinted with permission from the J. Biol. Regul. Homeost. Agents, 1993, 7: 9.

Fig. 3

Sedimentation rate of virus inhibitor from lamb brain tissue in a discontinuous sucrose gradient. Sucrose solutions in PBS, 5 mM MgC1₂, were used to form step gradients. Equivalent volumes of brain inhibitor preparation (0.5 ml) and 50% sucrose were mixed, layered on the discontinuous gradient, and centrifuged at 31 000 rev./min in a SW-55 rotor for 90 min. Collected fractions were examined for antiviral activity against Sindbis virus after extensive dialysis. Reprinted with permission from Antiviral Res., 1995, 27:380.

Fig. 4

Level of virus inhibitor in mouse brain extracts is unchanged during encephalitis. Three-week-old female outbred (ICR) mice were infected intraperitoneally with 3 LD₇₅ of BZV. Brains were harvested at days 3–6 postinfection, and homogenized. Virus inhibitory levels in the homogenates were titered against Sindbis virus, and are depicted in the bar graph (left Y axis). The rise in the virus titers in the brains and sera of infected mice (taken from Singh et al., 1989) are superimposed to illustrate the course of the BZV infections (○, virus load in brain; •, virus load per ml serum). Reprinted with permission from Antiviral Res., 1995, 27:384.

Fig. 5

Saliva interrupts the multiplication of human immunodeficiency virus (HIV) in infected human mononuclear leukocytes. *P<0.05 by Student's t-test. Reprinted with permission from Arch. Intern. Med., 1999, 159:306.

Fig. 6

Dilution in blood, milk, colostrums, and seminal fluid prevents saliva's inhibition of HIV multiplication in human PBL. *P<0.05 Student's t-test. Reprinted with permission from J. Infect. Dis., 2000, 181:500.