Murine cytomegalovirus retinitis during MAIDS: Susceptibility correlates with elevated intraocular levels of interleukin-4 mRNA.

Abstract

PURPOSE:

To determine if murine cytomegalovirus (MCMV)-infected eyes of mice with murine acquired immunodeficiency syndrome (MAIDS) that are destined to develop MCMV retinitis display elevated intraocular levels of interleukin-4 (IL-4) mRNA when compared with uninfected eyes of mice with MAIDS and unmanipulated, uninfected, eyes of normal healthy mice.

METHODS:

Groups of C57BL/6 mice with MAIDS and normal C57BL/6 mice were infected uniocularly with MCMV by subretinal MCMV injection. IL-4 levels in individual spleens collected five days later from groups of MAIDS mice and normal mice were assessed by quantitative ELISA. MCMV-infected eyes and uninfected contralateral eyes from another group of mice with MAIDS were also collected at five days postinfection and individually subjected to competitive RT-PCR assay and real-time RT-PCR assay for detection and quantification of IL-4 mRNA. Unmanipulated eyes from normal C57BL/6 mice served as controls.

RESULTS:

IL-4 mRNA was detected at a level of 9.7 +/- 3.4 pg mRNA per 1000 ng total RNA in 100% of MCMV-infected eyes of mice with MAIDS by competitive RT-PCR assay, but could not be detected in any of the uninfected eyes of MAIDS mice. In comparison, the more sensitive technique of real-time RT-PCR assay detected copies of IL-4 cDNA in both MCMV-infected eyes and uninfected eyes of MAIDS mice. MCMV-infected eyes showed a 16-fold increase in the number of IL-4 cDNA copies when compared with uninfected eyes. Neither technique detected IL-4 mRNA in unmanipulated eyes of normal mice. As expected, spleen cells from mice with MAIDS expressed significantly greater levels of IL-4 when compared with spleen cells from normal mice.

CONCLUSIONS:

MCMV-infected mice with MAIDS exhibited an expected preferential activation of Th2 cells as determined by increased levels of IL-4 in spleen cells when compared with spleen cells of normal mice. MCMV-infected eyes destined to develop retinitis during MAIDS also showed increased levels of detectable IL-4 mRNA when compared with uninfected eyes of mice with MAIDS. It is therefore possible that IL-4 synthesis by Th2 CD4+ T cells during retrovirus-induced immunosuppression serves to inhibit the perforin cytotoxic pathway that subsequently allows susceptibility to MCMV retinitis during MAIDS.

• Authors: Richard Dix, Scott Cousins
• Journal: Current eye research (Curr Eye Res) 2003 Mar-Apr Vol. 26 Issue 3-4 Pg. 211-7 ISSN: 0271-3683 [Print] England
• PMID: 12815549 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• RNA, Messenger
• Interleukin-4

Topics

• Animals
• Computer Systems
• Cytomegalovirus Retinitis (complications, metabolism, pathology)
• Disease Susceptibility
• Eye (metabolism)
• Herpesviridae Infections (complications, metabolism, pathology)
• Interleukin-4 (genetics, metabolism)
• Mice
• Mice, Inbred C57BL
• Murine Acquired Immunodeficiency Syndrome (complications, metabolism, pathology)
• Muromegalovirus
• RNA, Messenger (metabolism)
• Reverse Transcriptase Polymerase Chain Reaction
• Spleen (metabolism, pathology)