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Increased Virus Replication and Virulence after Serial Passage of Human Immunodeficiency Virus Type 2 in Baboons

Christopher P. Locher,^1, Stephanie A. Witt,¹ Brian G. Herndier,^2, Nancy W. Abbey,³ Klara Tenner-Racz,⁴ Paul Racz,⁴ Nancy B. Kiviat,⁵ Krishna K. Murthy,⁶ Kathleen Brasky,⁶ Michelle Leland,⁶ and Jay A. Levy^1*

Division of Hematology and Oncology, Department of Medicine, University of California, San Francisco, California 94143,¹ Department of Pathology, University of California, San Diego, La Jolla, California, 92103,² Department of Pathology, San Francisco General Hospital, San Francisco, California 94110,³ Department of Pathology and Koerber Laboratory for AIDS Research, Bernhard Nocht Institute for Tropical Medicine, D-20359 Hamburg, Germany,⁴ Department of Pathology, University of Washington, Seattle, Washington 98104,⁵ Southwest Foundation for Biomedical Research, San Antonio, Texas 78245⁶

Received 18 March 2002/ Accepted 27 September 2002

Similar to human immunodeficiency virus type 1 (HIV-1) infection of humans, the natural history of HIV-2 infection in baboons (Papio cynocephalus) is a slow and chronic disease that generally takes several years before an AIDS-like condition develops. To shorten the amount of time to the development of disease, we performed five serial passages of HIV-2_UC2 in baboons by using blood and bone marrow samples during the acute phase of infection when viral loads were at high levels. After these serial passages, virus levels in plasma, peripheral blood mononuclear cells (PBMC) and lymphatic tissues in the acutely infected baboons were increased. Within 1 year of the HIV-2 infection, all of the inoculated baboons showed specific signs of AIDS-related disease progression within the lymphatic tissues, such as vascular proliferation and lymphoid depletion. The HIV-2_UC2 recovered after four serial passages showed increased kinetics of viral replication in baboon PBMC and cytopathicity. This study suggests that the HIV-2 isolate recovered after several serial passages in baboons will be useful in future studies of AIDS pathogenesis and vaccine development by using this animal model.

Present address: Division of Vaccines, Maxygen, Inc., Redwood City, CA 94063.

Present address: Department of Pathology, University of California at San Diego, La Jolla, CA 92093.