HHV-8 DNA replication correlates with the clinical status in AIDS-related Kaposi’s sarcoma

Broccolo, Francesco; Din, Chiara Tassan; Viganò, Maria Grazia; Rutigliano, Teresa; Esposito, Susanna; Lusso, Paolo; Tambussi, Giuseppe; Malnati, Mauro S.

doi:10.1016/j.jcv.2016.02.019

Cited by 19 publications

(15 citation statements)

References 37 publications

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“…The study population did not differ in age and sex when compared to other studies evaluating PLWHA infected with HHV-8 [4, 8, 31–33]. Similarly, the median HIV viral load and TCD4 count did not show a statistically significant difference between the HIV/HHV-8 coinfected and the HIV monoinfected patients, corroborating works that also evaluated these clinical characteristics [31, 32, 34].…”

Section: Discussionsupporting

confidence: 81%

Mannose-binding lectin concentrations in people living with HIV/AIDS infected by HHV-8

et al. 2019

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BackgroundMannose-binding lectin (MBL) plays an important role in the innate immune response by activating the complement system via the lectin pathway, and it has been studied in several viral infections; however, the influence of MBL in PLWHA infected with HHV-8 is unknown. The objective of this study was to verify the association of MBL deficient plasma concentrations in HIV/HHV-8 coinfected and HIV monoinfected patients and to correlate these concentrations with HIV viral load and CD4 counts in both groups.ResultsThis was an analytical study of case-controls consisting of PLWHA monitored at the medical outpatient of Infectious and Parasitic Diseases of the clinical hospital in the Federal University of Pernambuco. Plasma concentrations of MBL were obtained by an enzyme-linked immunosorbent assay (ELISA) using a commercial Human Mannose Binding Lectin kit (MyBioSource, Inc.) that was performed according to the manufacturer’s guidelines, with values < 100 ng/ml considered deficient. A total of 245 PLWHA samples were analysed; 118 were HIV/HHV-8 coinfected and 127 were HIV monoinfected; 5.1% (6/118) of the coinfected patients and 3.2% (4/127) of the monoinfected patients (p = 0.445) were considered plasma concentration deficient. The median of the plasma concentrations of MBL in the coinfected patients was 2803 log10 ng/ml and was 2.959 log10 ng/ml in the monoinfected patients (p = 0.001). There was an inverse correlation between the plasma concentrations of MBL and the HIV viral load in both groups, but no correlation with the CD4 count.ConclusionsAlthough the plasma concentrations considered deficient in MBL were not associated with HHV-8 infection in PLWHA, the coinfected patients showed lower MBL concentrations and an inverse correlation with HIV viral load, suggesting that there may be consumption and reduction of MBL due to opsonization of HIV and HHV-8, leading to the reduction of plasma MBL and non-accumulation in the circulation.

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Section: Discussionsupporting

confidence: 81%

Mannose-binding lectin concentrations in people living with HIV/AIDS infected by HHV-8

et al. 2019

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“…LANA expression is therefore not confined to KS lesions [65, 71, 72]. KSHV DNAemia is commonly present in HIV+ patients with KS at the time of ART induction or with progressive KS, but undetectable in almost all patients on ART and those with regression of KS [19, 73]. …”

Section: Diagnosis and Pathologymentioning

confidence: 99%

Diagnosis and Treatment of Kaposi Sarcoma

2017

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Kaposi Sarcoma (KS) is the most common neoplasm of people living with HIV today. In Sub-Saharan Africa KS is among the most common cancers in men, overall. Not only HIV+ individuals present with KS; any immune compromised person infected with Kaposi Sarcoma-associated herpesvirus (KSHV) or human herpesvirus 8 is at risk: the elderly, children in KSHV-endemic areas, and transplant recipients. KS diagnosis is based on detection of the viral protein LANA in the biopsy, but not all cases of KS are the same or will respond to the same therapy. Standard KS therapy has not changed in 20 years, but newer modalities are on the horizon and will be discussed.

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“…Reactivation of the latent virus into productive lytic replication plays a pivotal role in the initiation and progression of KS, as viral load positively correlates with KS progression. Indeed, treatment of KS patients with antiherpesvirus drugs effectively leads to regression of KS tumors (2)(3)(4)(5)(6).…”

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confidence: 99%

High Glucose Induces Reactivation of Latent Kaposi's Sarcoma-Associated Herpesvirus

Zeng

Sha

et al. 2016

J Virol

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A high prevalence of Kaposi's sarcoma (KS) is seen in diabetic patients. It is unknown if the physiological conditions of diabetes contribute to KS development. We found elevated levels of viral lytic gene expression when Kaposi's sarcoma-associated herpesvirus (KSHV)-infected cells were cultured in high-glucose medium. To demonstrate the association between high glucose levels and KSHV replication, we xenografted telomerase-immortalized human umbilical vein endothelial cells that are infected with KSHV (TIVE-KSHV cells) into hyperglycemic and normal nude mice. The injected cells expressed significantly higher levels of KSHV lytic genes in hyperglycemic mice than in normal mice. We further demonstrated that high glucose levels induced the production of hydrogen peroxide (H 2 O 2 ), which downregulated silent information regulator 1 (SIRT1), a class III histone deacetylase (HDAC), resulting in the epigenetic transactivation of KSHV lytic genes. These results suggest that high blood glucose levels in diabetic patients contribute to the development of KS by promoting KSHV lytic replication and infection. IMPORTANCEMultiple epidemiological studies have reported a higher prevalence of classic KS in diabetic patients. By using both in vitro and in vivo models, we demonstrated an association between high glucose levels and KSHV lytic replication. High glucose levels induce oxidative stress and the production of H 2 O 2 , which mediates the reactivation of latent KSHV through multiple mechanisms. Our results provide the first experimental evidence and mechanistic support for the association of classic KS with diabetes. K aposi's sarcoma (KS) is a vascular neoplasia etiologically associated with Kaposi's sarcoma-associated herpesvirus (KSHV) infection (1). KSHV establishes a lifelong persistent latent infection following acute infection. Reactivation of the latent virus into productive lytic replication plays a pivotal role in the initiation and progression of KS, as viral load positively correlates with KS progression. Indeed, treatment of KS patients with antiherpesvirus drugs effectively leads to regression of KS tumors (2-6).Unlike iatrogenic or AIDS-associated KS, classic KS occurs predominantly in elderly men of Mediterranean or Jewish descent who have no apparent immune suppression (7). The exact cause of the development of classic KS remains undefined. Asthma, allergies in males, topical corticosteroid use, and infrequent bathing have been suggested to be risk factors for classic KS (8,9). Multiple studies have also documented a high prevalence of classic KS in patients with diabetes mellitus (10-13), a metabolic syndrome that manifests with elevated levels of blood glucose and episodic ketoacidosis, due to either a lack of insulin (type 1 diabetes) or cellular resistance to insulin (type 2 diabetes). High levels of KSHV DNA and seropositivity have been seen in diabetic patients (14-16). However, no study has ever determined if diabetes is the cause or an effect of KS and whether high glucose levels play ...

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HHV-8 DNA replication correlates with the clinical status in AIDS-related Kaposi’s sarcoma

Cited by 19 publications

References 37 publications

Mannose-binding lectin concentrations in people living with HIV/AIDS infected by HHV-8

Mannose-binding lectin concentrations in people living with HIV/AIDS infected by HHV-8

Diagnosis and Treatment of Kaposi Sarcoma

High Glucose Induces Reactivation of Latent Kaposi's Sarcoma-Associated Herpesvirus

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