Latency-associated nuclear antigen expression and human herpesvirus-8 polymerase chain reaction in the evaluation of Kaposi sarcoma and other vascular tumors in HIV-positive patients

Abstract

Human herpesvirus-8 (HHV-8) latency-associated nuclear antigen (LANA) is expressed in endothelial and spindle cells of nearly all Kaposi sarcomas, and the presence of this antigen in serum is strongly correlated with the risk of developing Kaposi sarcoma in immunocompromised individuals. Studies of vascular tumors occurring in the general population show LANA expression to be specific for Kaposi sarcoma. No study to date, however, has examined whether non-Kaposi sarcoma vascular tumors arising in immunocompromised patients may express LANA, possibly reflecting origin from an HHV-8-infected endothelial progenitor cell. The objective of this study was to evaluate the specificity of LANA expression for Kaposi sarcoma in immunocompromised patients by LANA immunohistochemistry and real-time polymerase chain reaction (PCR) for HHV-8. A total of 13 cases of non-Kaposi sarcoma vascular tumors (12 hemangiomas and one epithelioid hemangioendothelioma) and 24 cases of Kaposi sarcoma, all from known HIV-positive patients, were immunostained for LANA and evaluated for the presence of HHV-8 DNA by real-time PCR. LANA expression was seen in 22 of 24 (92%) of Kaposi sarcoma cases and in 0 of 13 non-Kaposi sarcoma cases. Real-time PCR detected HHV-8 in all of the Kaposi sarcoma cases and in four of the non-Kaposi sarcoma cases (all hemangiomas). LANA expression appears to be a highly sensitive and specific marker of Kaposi sarcoma in both the general population and in HIV-positive patients. This is in contrast to HHV-8 PCR, which is positive in a small subset of non-Kaposi sarcoma vascular tumors, most likely due to detection of HHV-8 within intratumoral blood mononuclear cells by the highly sensitive real-time PCR technique. For this reason, LANA immunohistochemistry is preferable to HHV-8 PCR for the evaluation of problematic vascular proliferations in HIV-positive individuals.

Asynchronous Progression through the Lytic Cascade and Variations in Intracellular Viral Loads Revealed by High-Throughput Single-Cell Analysis of Kaposi's Sarcoma-Associated Herpesvirus Infection

“…Following initial infection, KSHV, like all herpesviruses, assumes a prolonged period of latency. Lytic reactivation of the virus, however, is a critical phase in viral pathogenesis, as it leads to progeny virion production, horizontal spread, and viral transmission, as well as the expression of potentially pathogenic lytic genes (17). To explore the ability of MIFC to differentiate between the phases of viral reactivation, we chemically induced the latently infected primary effusion lymphoma cell line BCBL-1 with valproic acid and measured expression of the essential latent protein, LANA; the lytic switch protein, RTA; and the late lytic marker, K8.1, at hours 0, 24, 48, and 72 ( Fig.…”

“…Importantly, KSHV-infected cultures usually exhibit spontaneous lytic replication, where 1 to 5% of cells have entered the lytic gene cascade (39). Assays on pooled samples, such as DNA array, quantitative real-time PCR, and immunoblots, by default, include both latent and lytic subpopulations, thereby obscuring experimental analyses (8,17,32,43). Since gene expression in lytically infected cells is robust and involves a wide range of genes, the coexistence of the two states of infection precludes a precise characterization of the viral transcriptomes (latent and lytic).…”

Human Herpesvirus-8 Infection of Primary Pulmonary Microvascular Endothelial Cells

“…This association has been challenged based on the lack of serologic evidence of HHV-8 infection in patients with IPAH, as well as on the inability of other investigators to confirm PCR evidence of viral open reading frames (ORFs) within the lung parenchyma of patients with IPAH (33)(34)(35). It is notable, however, that immunohistochemical staining for LANA-1 is an accepted means of identifying HHV-8 infection in tissue samples (36). It is also notable that the percentage of LANA-1-positive staining in lung tissue of patients with IPAH (61.5%) reported by other groups was the same as reported by Cool and colleagues (62%) in which both LANA-1 staining and a PCR assay for ORF-72, the viral cyclin gene of HHV-8, was positive (32).…”

Gastrointestinal tract spindle cell lesions—just like real estate, it's all about location

“…[22][23][24][25] Virtually all examples show nuclear labeling with HHV-8 antibodies (Figure 3c). 26 An important pitfall for the pathologist is to beware that KS often immunolabels with CD117 antibodies (Figure 3d). …”