MYOPATHY AND SPONTANEOUS PASTEURELLA PNEUMOTROPICA-INDUCED ABSCESS FORMATION IN AN HIV-1 TRANSGENIC MOUSE MODEL

In an effort to augment human immunodeficiency virus type 1 (HIV-1) ge ne expression in transgenic mice, an infectious proviral DNA clone was modified by deleting the two NF kappa B binding sites and some adjace nt upstream LTR sequences and replacing them with the core enhancer of Moloney murine leukemia virus (MLV). Two independent lines of MLV/HIV transgenic mice were established that expressed HIV-1-specific RNA in lymphoid tissue, striated skeletal muscle, and the eye lens. Heterozy gous animals from each transgenic line spontaneously developed an infl ammatory disease of the eye associated with the production of copious amounts of purulent lacrimal secretions beginning at 2 weeks of age. P eriorbital abscess formation became grossly apparent by 2 months of ag e and Pasteurella pneumotropica was cultured from the harderian glands and conjunctival surfaces of many of the MLV/HIV animals but not thei r nontransgenic, cohabiting littermates. This gram-negative commensal bacterium has been previously associated with a similar disease phenot ype in immunocompromised (e.g., nude mice) rodent colonies. MLV/HIV mi ce developed normally until 15 weeks of age, when weight loss and wast ing occurred, culminating in premature death (as earlier as 6 months o f age). The cachexia was associated with an initially focal and subseq uently progressive myopathy, coinciding with age-related increases of HIV gene expression in muscle.