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Journal of Virology, May 2000, p. 4505-4511, Vol. 74, No. 10
0022-538X/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.

Inhibition of Human Immunodeficiency Virus Type 1 Replication prior to Reverse Transcription by Influenza Virus Stimulation

Ligia A. Pinto,1 Vesna Blazevic,1 Bruce K. Patterson,2 C. Mac Trubey,3 Matthew J. Dolan,4 and Gene M. Shearer1,*

Experimental Immunology Branch, National Cancer Institute, National Institutes of Health, Bethesda,1 andIntramural Research Support Program, SAIC Frederick, NCI-FCRDC, Frederick,3 Maryland; Laboratory of Viral Pathogenesis, Northwestern University Medical School, Chicago, Illinois2; and Wilford Hall Medical Center, Lackland AFB, Texas4

Received 27 September 1999/Accepted 11 February 2000

It is now recognized that, in addition to drug-mediated therapies against human immunodeficiency virus type 1 (HIV-1), the immune system can exert antiviral effects via CD8+ T-cell-generated anti-HIV factors. This study demonstrates that (i) supernatants from peripheral blood mononuclear cells (PBMC) stimulated with influenza A virus inhibit replication of CCR5- and CXCR4-tropic HIV-1 isolates prior to reverse transcription; (ii) the HIV-suppressive supernatants can be generated by CD4- or CD8-depleted PBMC; (iii) this anti-HIV activity is partially due to alpha interferon (IFN-alpha ), but not to IFN-gamma , IFN-beta , the beta -chemokines MIP-1alpha , MIP-1beta , and RANTES, or interleukin-16; (iv) the anti-HIV activity is generated equally well by PBMC cultured with either infectious or UV-inactivated influenza A virus; and (v) the antiviral activity can be generated by influenza A-stimulated PBMC from HIV-infected individuals. These findings represent a novel mechanism for inhibition of HIV-1 replication that differs from the previously described CD8 anti-HIV factors (MIP-1alpha , MIP-1beta , RANTES, and CD8 antiviral factor).

* Corresponding author. Mailing address: Experimental Immunology Branch, National Institutes of Health, NCI, Bldg. 10, Rm. 4B36, Bethesda, MD 20892. Phone: (301) 402-3246. Fax: (301) 402-3643. E-mail: shearerg{at}exchange.nih.gov.

Journal of Virology, May 2000, p. 4505-4511, Vol. 74, No. 10
0022-538X/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.


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