Fang L, Howett MK; International Conference on AIDS (15th : 2004 : Bangkok, Thailand).

Int Conf AIDS. 2004 Jul 11-16; 15: abstract no. ThPeA6957.

Drexel University, Philadelphia, United States

Background: Subcutaneous xenografts of human epithelial tissues in immuno-compromised mice demonstrate accurate tissue differentiation phenotypes and long-term viability. Human immunodeficiency virus type 1 (HIV-1), human papillomaviruses (HPV) and herpes simplex virus type 2 (HSV-2) replicate in these xenografts when they are established using human vagina. Xenografts that had been previously infected with HPV type 11 for three months and exhibiting papillomatous morphology and HPV replication could be super-infected with HSV-2. This in vivo approach paralleled in vitro methods to examine co-infection. Methods: Subcutaneous grafts of vagina were established in athymic mice and infected at one week with HPV 11. Infected animals were kept for three months to allow development of human papilloma. Super-infection of papillomas with HSV-2 was then carried out; control papillomas were sham inoculated. Parallel in vitro systems allowed transient expression of HPV 11 followed by super-infection with HSV-2. Determinants of infection included measurement of HPV RNA transcripts and DNA and morphology of the papillomas. HSV-2 DNA and cytopathology was also measured. Results: HSV-2 super-infection of HPV 11 infected cells resulted in specific decreases in the HPV 11 transcripts in in vitro and in vivo systems. In vitro these effects were mediated by the virus host shut-off (vhs) protein of HSV-2 because vhs-negative mutants could not mediate transcriptional repression. Cloning and gene delivery of vhs is in progress. HSV-2 protein synthesis was not required for the transcriptional shut-off. Examination of the doubly infected xenografts indicated that areas actively replicating HSV-2 had become negative for HPV 11 nucleic acid signal. Conclusions: Our results demonstrate that infectious or defective HSV-2 virions mediate potent effects on human papillomas and their endogenous HPV genomes. These interactions may alter the biological course of papilloma development. Further studies will examine interactions of HIV-1 and HSV-2 in these same models.

Publication Types:

• Meeting Abstracts

Keywords:

• Animals
• Female
• HIV-1
• Herpesvirus 2, Human
• Humans
• In Vitro
• Mice
• Mice, Nude
• Papillomaviridae
• Virion
• virology

Other ID:

• GWAIDS0036525

UI: 102280741

From Meeting Abstracts