In vivo cell and tissue tropism of SIVsmmPBj14-bcl.3

To gain insight into the unique pathogenicity of simian immunodeficiency vi rus (SIV) variant PBj14 which produces an acutely lethal enteropathic syndr ome in infected pigtail macaques, we investigated the cell and tissue tropi sms of a highly pathogenic biologic clone (bcl.3) of SIVsmmPBj14. To compar e the relative amount of viral antigen in lymphoid organs of infected macaq ues we used an objective semiquantitative immunohistochemistry (sQIHC) assa y. We found that in all animals viral antigen load was greater in alimentar y-associated lymphoid tissues (gut-associated lymphoid tissue [GALT], tonsi l, mesenteric and retropharyngeal lymph nodes) than in non-alimentary-assoc iated lymphoid tissues (spleen, thymus, inguinal and axillary lymph nodes). Moreover, in six of nine animals examined, virus load in GALT was greater than that in any other lymphoid tissue. To determine whether the acute path ogenicity and prolific replication of SIVsmmPBj14 might be explained by a b roader in vivo cell tropism than is typical of SIVs, we used cell subset se paration and nested PCR, We found that the primary target cells in mesenter ic lymph node for SIVsmmPBj14 were CD4(+) T lymphocytes, However, the virus also infected macrophages, as well as CD8(+) T cells and B cells, albeit a t low frequencies. These results suggest that alimentary lymphoid tissue lo calization rather than unusual cell phenotype tropism distinguishes the sin gular pathogenesis of SIVsmmPBj14.