Background: The lack convenient and inexpensive small animal model of HIV infection hampers significantly the research on immunopathogenesis, antiviral drugs, and vaccines.

Objectives: Development of HIV model in small animals, i.e., cotton rats, was undertaken.

Study Design: Cotton rats of both sexes were exposed to highly replicating HIV-1(zmb) strain by intraperitonial and retrobulbar routes. The infection was evaluated by morphological and clinical criteria and by amplification of HIV DNA integrated in animal tissues.

Results: Six months after intraperitoneal infection the lymphoid tissues of all inoculated animals exhibited integrated proviral DNA. Despite viral integration no active systemic HIV replication was observed. Brain and spleen morphological changes indicated the presence of the inflammatory reaction, which was followed by a degenerative process. Clinical manifestations of the infection, while varied, revealed relative weight loss at three months after infection; apparent respiratory disorders; and death of some animals with signs of cachexia and alopecia.

Conclusions: Clinical, morphological, and virology assessment of infected animals indicate that the virus crosses the interspecies barrier and cotton rats can be used as a small animal model of HIV infection.

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