Vitamin A In Milk Can Potentially Reduce The Replication Of Enveloped Viruses In Infants

Isaacs, C.E.1, Xu, W.1, Kascsak, R.2,Pullarkat, R.1

'Department of Developmental Biochemistry, 2Department of Virology, New York State Institute for Basic Research in Developmental Disabilities, Staten Island, NY 10314, USA

Vitamin A (retinol and its derivatives) and provitamin A carotenoids are fat soluble compounds which play a role in maintenance and restoration of epithelial barriers, stimulation of immune function and provide increased resistance to gastrointestinal and respiratory infections1. Diarrhea, measles and in some studies respiratory infections are common in vitamin A deficient children2. Although most studies indicate that vitamin A status does not reduce the incidence of infectious disease, the severity of some infections, especially those related to diarrhea can be reduced with vitamin A supplementation. Vitamin A present in human milk may help to reduce the severity of viral infections since these infections appear to alter the normal transport and metabolism of retinol. The results presented in this and previous studies3 show that vitamin A can reduce the production of infectious enveloped virus particles in cultured cells and suggest a direct antiviral effect of vitamin A in vivo which is not mediated by immune function.

In the present study the application of retinoic acid, the acid form of vitaminA, inhibited the production of a number of different enveloped viruses regardless of whether they were DNA (herpes simplex virus-1 (HSV-1)) or RNA (measles and vesicular stomatitis virus (VSV)) viruses (Table). Decreases in viral titers ranged from 1,000-foldto as much as 100,000-fold. HSV-1 titers were reduced by similar amounts in both monkey kidney cells and in a differentiated human neuroblastoma cell line (SY5Y) which is similar to the neuronal cells that HSV-1 infects in vivo. Retinoic acid treatment did not interfere with the replication of nonenveloped viruses as evidenced by the results with poliol and polio 3 viruses in both monkey kidney and an epithelial cell line.

Treatment of HSV-1 infected Vero cells with retinoic acid did not reduce the production of viral glycoproteins, even when the production of infectious virus particles was inhibited by 1,000-fold. Envelope glycoproteins are a constituent of all enveloped viruses and inhibition of their synthesis would have been one possible mechanism for vitamin A dependent reduction in viral infectivity. Studies done using labeled carbohydrates however, suggest that retinoic acid treatment interferes with the processing of carbohydrates attached to enveloped virus proteins. These studies indicate that the maintenance of adequate vitamin A levels in breast milk could help to reduce the severity of enveloped virus infections in infants when a vaccine is not available.

Table 1. Susceptibility of Enveloped and Nonenveloped Viruses to Inhibition by Retinoic

Acid

Virus1

Envelope

Cell Type2

Control

Retinoic Acid

Measles

Y

Vero

105.00

10125

HSV-1

Y

Vero

106. 90

101.40

HSV-1

Y

SY5Y

105.50

10°.63

VSV

Y

Vero

108.50

102.75

Polio 1

N

ME 180

10300

10325 5.25

Polio 3

N

LLC

10550

10

'Herpes simplex virus-1 (HSV-1); VSV (vesicular stomatitis virus). 2Vero (monkey kidney); SY5Y (human neuroblastoma); ME 180 (human cervical epithelial carcinoma); LLC (monkey kidney). 3Viral titer numbers are tissue culture infectious doses (log10).

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