Immature and transitional B cells are latency reservoirs for a gammaherpesvirus

J Virol. 2010 Dec;84(24):13045-52. doi: 10.1128/JVI.01455-10. Epub 2010 Oct 6.

Abstract

Gammaherpesviruses, including Kaposi's sarcoma-associated herpesvirus (KSHV; also known as human herpesvirus 8 [HHV-8]), Epstein-Barr virus (EBV), and murine gammaherpesvirus 68 (MHV68; also known as gammaherpesvirus 68 [γHV68] or murine herpesvirus 4 [MuHV-4]), establish lifelong latency in the resting memory B cell compartment. However, little is known about how this reservoir of infected mature B cells is maintained for the life of the host. In the context of a normal immune system, the mature B cell pool is naturally maintained by the renewable populations of developing B cells that arise from hematopoiesis. Thus, recurrent infection of these developing B cell populations could allow the virus continual access to the B cell lineage and, subsequent to differentiation, the memory B cell compartment. To begin to address this hypothesis, we examined whether MHV68 establishes latency in developing B cells during a normal course of infection. In work described here, we demonstrate the presence of viral genome in bone marrow pro-pre-B cells and immature B cells during early latency and immature B cells during long-term latency. Further, we show that transitional B cells in the spleen are latently infected and express the latency-associated nuclear antigen (LANA) throughout chronic infection. Because developing B cells normally exhibit a short life span and a high rate of turnover, these findings suggest a model in which gammaherpesviruses may gain access to the mature B cell compartment by recurrent seeding of developing B cells.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens, Viral / metabolism*
  • B-Lymphocytes / immunology
  • B-Lymphocytes / virology*
  • Herpesviridae Infections / virology*
  • Humans
  • Mice
  • Mice, Inbred C57BL
  • Nuclear Proteins / metabolism*
  • Precursor Cells, B-Lymphoid / immunology
  • Precursor Cells, B-Lymphoid / virology*
  • Rhadinovirus / pathogenicity
  • Rhadinovirus / physiology*
  • Spleen / immunology
  • Spleen / virology
  • Tumor Virus Infections / virology*
  • Virus Activation
  • Virus Latency*
  • Virus Replication

Substances

  • Antigens, Viral
  • Nuclear Proteins
  • latency-associated nuclear antigen