Pulmonary vascular lesions are common in SIV- and SHIV-env-infected macaques.
The lack of animal models of HIV-related pulmonary arterial hypertension (HIV-PAH) severely limits investigation of this serious disease. While histological evidence of HIV-PAH has been demonstrated in macaques infected with simian immunodeficiency virus (SIV) as well as with chimeric simian/human immunodeficiency virus (SHIV) containing HIV-1-derived Nef protein, other primate models have not been studied. The objective was to document and describe the development of pulmonary vascular changes in macaques infected with SIV or with SIV containing HIV-1-derived envelope protein (SHIV-env). Lung tissue was obtained at necropsy from 13 SHIV (89.6P)-env-infected macaques and 10 SIV (ΔB670)-infected macaques. Pulmonary arterial pathology, including arterial hyperplasia and the presence of plexiform lesions, was compared to normal monkey lung. Pulmonary artery hyperplasia was present in 8 of 13 (62%) SHIV-env-infected macaques and 4/10 (36%) SIV-infected macaques. The most common histopathological lesions were intimal and medial hyperplasia of medium and large pulmonary arteries. Hyperplastic lesions were predominantly due to smooth muscle cell hyperplasia. This is the first report of pulmonary vascular lesions in SHIV-env-infected macaques and confirms prior reports of pulmonary vasculopathy in SIV-infected macaques. The finding of pulmonary arteriopathy in monkeys infected with SHIV not containing HIV-nef suggests that other factors might also be important in the development of HIV-PAH. This SHIV-env model provides a new means to investigate HIV-PAH.
George
M Patricia
MP
Department of Medicine, University of Pittsburgh, Pennsylvania 15213, USA. georgemp2@upmc.edu
Brower
Alexandra
A
Kling
Heather
H
Shipley
Tim
T
Kristoff
Jan
J
Reinhart
Todd A
TA
Murphey-Corb
Michael
M
Gladwin
Mark T
MT
Champion
Hunter C
HC
Morris
Alison
A
Norris
Karen A
KA
D000818:Animals; D001808:Blood Vessels / Q000473:pathology*; D001992:Bronchoalveolar Lavage Fluid; D006678:HIV / Q000302:isolation & purification*; D007150:Immunohistochemistry; D008168:Lung / Q000098:blood supply*; D008252:Macaca fascicularis; D008253:Macaca mulatta; D015302:Simian Immunodeficiency Virus / Q000302:isolation & purification*