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Journal of Virology, November 2002, p. 11460-11468, Vol. 76, No. 22
0022-538X/02/$04.00+0     DOI: 10.1128/JVI.76.22.11460-11468.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.

Antibody to a Lytic Cycle Viral Protein Decreases Gammaherpesvirus Latency in B-Cell-Deficient Mice

Shivaprakash Gangappa,1 Sharookh B. Kapadia,1 Samuel H. Speck,2* and Herbert W. Virgin IV1*

Department of Pathology and Immunology, Washington University School of Medicine, Saint Louis, Missouri 63110,1 Division of Microbiology and Immunology, Yerkes Regional Primate Research Center, Emory University, Atlanta, Georgia 303292

Received 20 May 2002/ Accepted 14 August 2002

While antiviral antibody plays a key role in resistance to acute viral infection, the contribution of antibody to the control of latent virus infection is less well understood. Gammaherpesvirus 68 ({gamma}HV68) infection of mice provides a model well suited to defining contributions of specific immune system components to the control of viral latency. B cells play a critical role in regulating {gamma}HV68 latency, but the mechanism(s) by which B cells regulate latency is not known. In the experiments reported here, we determined the effect of passively transferred antibody on established {gamma}HV68 latency in B-cell-deficient (B-cell-/-) mice. Immune antibody decreased the frequency of cells reactivating ex vivo from latency in splenocytes (>10-fold) and peritoneal cells (>100-fold) and the frequency of cells carrying latent viral genome in splenocytes (>5-fold) and peritoneal cells (>50-fold). This effect required virus-specific antibody and was observed when total and virus-specific serum antibody concentrations in recipient B-cell-/- mice were <8% of those in normal mice during latent infection. Passive transfer of antibody specific for the lytic cycle {gamma}HV68 RCA protein, but not passive transfer of antibody specific for the v-cyclin protein or the latent protein M2, decreased both the frequency of cells reactivating ex vivo from latency and the frequency of cells carrying the latent viral genome. Therefore, antibody specific for lytic cycle viral antigens can play an important role in the control of gammaherpesvirus latency in immunocompromised hosts. Based on these findings, we propose a model in which ongoing productive replication is essential for maintaining high levels of latently infected cells in immunocompromised hosts. We confirmed this model by the treatment of latently infected B-cell-/- mice with the antiviral drug cidofovir.

* Corresponding author. Mailing address for Samuel H. Speck: Division of Microbiology and Immunology, Yerkes Regional Primate Research Center, Emory University, 954 Gatewood Rd., NE, Atlanta, GA 30329. Phone: (404) 727-7665. Fax: (404) 727-7768. E-mail: sspeck{at}rmy.emory.edu. Mailing address for Herbert W. Virgin IV: Department of Pathology and Immunology, Washington University School of Medicine, Box 8118, 660 South Euclid Ave., Saint Louis, MO 63110. Phone: (314) 362-9223. Fax: (314) 362-4096. Mailing address for Herbert W. Virgin IV: Department of Pathology and Immunology, Washington University School of Medicine, Box 8118, 660 South Euclid Ave., Saint Louis, MO 63110. Phone: (314) 362-9223. Fax: (314) 362-4096. E-mail: virgin{at}immunology.wustl.edu.

Journal of Virology, November 2002, p. 11460-11468, Vol. 76, No. 22
0022-538X/02/$04.00+0     DOI: 10.1128/JVI.76.22.11460-11468.2002
Copyright © 2002, American Society for Microbiology. All Rights Reserved.



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