student research day - Case Western Reserve University School of ...

GEORGE ANESI
HIV-1 negative factor (Nef) protein in Kaposi’s sarcoma
George L. Anesi, BS, MS-II, Ethel Cesarman, MD, PhD
Department of Pathology and Laboratory Medicine
Weill Cornell Medical College, New York, NY
Infection with the human immunodeficiency virus-1 (HIV-1) predisposes patients to Kaposi’s sarcoma (KS), a
vascular tumor caused by the Kaposi’s sarcoma–associated herpesvirus (KSHV), also known as human
herpesvirus 8 (HHV-8). Independent KSHV infection confers far less risk of developing KS versus KSHV
coinfection with HIV-1 which shows a dramatically increased risk of tumor development reported at up to 50% at
10 years. This increased risk is beyond what would be expected with immunodeficiency alone. It seems to not be
KSHV infection alone that leads to KS but rather also an environment conducive to KSHV replication and
transformation provided by HIV-1. KS cells contain the KSHV genome, but not the HIV genome, so an effect
would have to be indirect or produced by a secreted HIV protein. HIV-1 negative factor (Nef) protein is produced
by HIV-1 and required for viral replication and plays a significant, though not entirely understood role, in its
attack on the host. Specifically, Nef is protective for infective cells against cytotoxic T lymphocyte attack and
apoptosis. Infected cells release Nef into the extracellular environment and it has been shown that Nef is taken
up by B cells. We hypothesize that Nef could play a role in the transformation of KSHV-infected cells and as such
could contribute to the dramatic increase in risk of KS development in HIV-1/KSHV coinfection versus KSHV
infection alone. We analyzed skin and lymph node tissue biopsies of KS lesions from HIV-1-positive patients for
the distribution of the HIV-1 Nef protein. We used immunofluorescence to demonstrate the presence of HIV-1
Nef in cells positive for the KSHV protein latency-associated nuclearantigen (LANA), currently unreported in the
literature. LANA-positivity indicates that these Nef+ cells are indeed KSHV infected and further analysis
confirmed these cells were also CD34+ suggesting endothelial derivation consistent with the vascular, spindle
cell lesions of KS. Further research must be done to evaluate what regulatory role HIV-1 Nef plays in KSHV-
infected cells and in KS development.
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