For the Future Studies of Kaposi’s Sarcoma-Associated Herpesvirus

2012

Keiji Ueda

It is 18 years since Kaposi’s sarcoma-associated virus (KSHV), also called human herpesvirus 8 (HHV-8), was found from Kaposis’ sarcoma (KS) by Chang et al. (1994). More than 8, 000 reports have been published so far and we have learned many things from this virus. I would like to say it is about time to look back previous studies and to think what to study next on the virus, and planed a topic to think what to study next on the virus for future.

Herpesviruses have relatively big genomes and encode a 100 genes or so. Thus, the virion assembly/structure, gene expression regulation and attachment/entry are complicated and have known only an iceberg of them. Studying the details how the viruses run their life cycles and cause diseases in their processes will lead to exploring new therapeutic drugs/methods.

A viral life cycle starts from attachment on the susceptible cells and then, entry into the cells, followed by the viral gene expression, the genome replication, the particle assembly and finally the daughter viruses egress out of the cells. This process is skillfully built and all the viral genes are required for the process, though there are essential genes and non-essential ones. Viral pathogenesis could be established during this process by the interaction between viruses and host cells, and individual host systems such as immune system. In this topic, although I would like to cover all the processes, thankfully, 15 specialists in each field have contributed for this topic.

see full text article:  NIH

Disseminated cutaneous Kaposi sarcoma in a patient receiving triptolide/tripdiolide for rheumatoid arthritis.

Aug  2012

Grzegorzewska AE, Frankiewicz D, Bręborowicz D, Matławska I, Bylka W.

Source

Chair and Department of Nephrology, Transplantology and Internal Diseases, Karol Marcinkowski University of Medical Sciences, Poznan, Poland. alicja_grzegorzewska@yahoo.com

Abstract

BACKGROUND:

To date, Kaposi sarcoma has not been mentioned among the adverse effects of triptolide/tripdiolide, ethyl acetate extracts or polyglycosides of the Chinese herbal remedy Tripterygium wilfordii Hook F.

CASE REPORT:

A patient was diagnosed with rheumatoid arthritis at the age of 29 years. She underwent treatment with corticosteroids, methotrexate and gold sodium thiosulfate, and was chronically taking ketoprofen. At the age of 59 years she started to take a powder (≈2 g/day) from a Chinese physician for treatment of rheumatoid arthritis. This powder was supplied to her regularly for 10 years. At the age of 69 years, multiple soft, violaceous to dark-red patches, plaques, nodules and blisters of varying sizes appeared on a background of severely edematous skin on her legs, and later on her arms. Biopsy specimens of the leg lesions were diagnostic for human herpesvirus 8-associated Kaposi sarcoma. Triptolide (235 µg/1 g) and tripdiolide were found in the Chinese powder by the use of Liquid Chromatography Electrospray Ionization Mass Spectrometry. Administration of the powder was stopped and medication with paclitaxel was introduced. General condition of the patient improved and skin lesions diminished significantly.

CONCLUSIONS:

This case indicates a possible association between triptolide/tripdiolide chronic intake and development of human herpesvirus 8-associated Kaposi sarcoma. Triptolide/tripdiolide could contribute to development of Kaposi sarcoma by reactivation of latent human herpesvirus 8, permitted by immunosuppression induced by triptolide.

PubMed

AIDS-related Gastrointestinal Kaposi Sarcoma in Korea: A Case Report and Review of the Literature.

Sept 2012

Chung CY, Park SW, Myung E, Cho DK, Song YA, Park KJ, Jang HC, Joo YE.

Source

Department of Internal Medicine, Chonnam National University Medical School, 8 Hak-dong, Dong-ku, Gwangju 501-757, Korea.

Abstract

Kaposi sarcoma (KS) is a vascular neoplasm, which is fairly prevalent in acquired immunodeficiency syndrome (AIDS) patients. Mucocutaneous and lymph node involvements are characteristic features of KS in AIDS patients. The involvement of gastrointestinal tract occurs in 40% of KS patients and leads to significant morbidity and mortality. In the highly active antiretroviral therapy (HAART) era, the rate of AIDS related KS has fallen with control of human immunodeficiency virus (HIV) viremia. However, it is still recognized as the primary AIDS-defining illness, and the proportion of AIDS diagnoses made due to KS ranged from 4.1% to 7.5%. In Korea, AIDS-related KS has been report in low rate incidence. Its gastrointestinal involvements are rarely reported. To date, five cases have been recorded in Korea. Herein, we present an additional case of gastrointestinal KS as the AIDS-defining illness and review of the Korean medical literature. (Korean J Gastroenterol 2012;60:166-171).

KJG

Oral HIV-Associated Kaposi Sarcoma: A Clinical Study from the Ga-Rankuwa Area, South Africa.

2012

Khammissa RA, Pantanowitz L, Feller L.

Source

Department of Periodontology and Oral Medicine, University of Limpopo, Medunsa Campus, Pretoria 0204, South Africa.

Abstract

Background. Kaposi sarcoma (KS) is one of the most common neoplasms diagnosed in HIV-seropositive subjects. Oral involvement is frequent and is associated with a poor prognosis. The aim of this study was to characterize the features of oral HIV-KS in patients from Ga-Rankuwa, South Africa. 

Methods. All cases with confirmed oral HIV-KS treated at the oral medicine clinic in Ga-Rankuwa from 2004 to 2010 were included in this retrospective study. Differences between males and females with oral HIV-KS in relation to HIV infection status, to oral KS presentation and to survival rates were statistically analysed. 

Results. Twenty (54%) of the 37 patients in the study were females and 17 (46%) were males. In 21 patients (57%), the initial presentation of HIV-KS was in the mouth. Other than the fact that females presented with larger (≥10 mm) oral KS lesions (P = 0.0004), there were no statistically significant gender differences. Significantly more patients presented with multiple oral HIV-KS lesions than with single lesions (P = 0.0003). Nine patients (24%) developed concomitant facial lymphoedema, and these patients had a significantly lower CD4+ T-cell count (28 cells/mm(3)) compared to the rest of the group (130 cells/mm(3)) (P = 0.01). The average CD4+ T-cell count of the patients who died (64 cells/mm(3)) was significantly lower (P = 0.0004), there were no statistically significant gender differences. Significantly more patients presented with multiple oral HIV-KS lesions than with single lesions (P = 0.016) at the time of oral-KS presentation than of those who survived (166  cells/mm(3)). 

CONCLUSIONS: In Ga-Rankuwa, South Africa where HIV-KS is prevalent, oral KS affects similarly males and females. A low CD4+ T-cell count at the time of oral HIV-KS diagnosis and the development of facial lymphoedema during the course of HIV-KS disease portends a poor prognosis.

NIH

Pulmonary kaposi sarcoma in AIDS.

October 2012

Sumedh S. Hoskote, MD AFFILIATIONS  Department of Medicine, St. Luke's-Roosevelt Hospital Center, Columbia University College of Physicians and Surgeons, New York, NY , Vishal P. Patel, DO Division of Pulmonary, Critical Care and Sleep Medicine Columbia University College of Physicians and Surgeons, New York, NY

A 34-year-old man presented to the hospital with a productive cough, dyspnea, subjective fever, chills, and myalgias. Fever, tachycardia, tachypnea, and severe hypoxemia were noted on arrival. Examination revealed a frail, diaphoretic man in considerable respiratory distress, with diffuse bilateral rales and rhonchi; a violaceous, raised rash over the limbs and trunk was also noted. Findings on chest radiography were suggestive of multilobar pneumonia. A rapid oral antibody test for human immunodeficiency virus (HIV) returned a positive result.

Computed tomography of the chest showed striking flame-shaped opacities and spicular thickening of the bronchovascular bundles in all lobes (panels A, B, and C, arrows). These findings are characteristic of pulmonary Kaposi sarcoma (KS).¹ In our patient, the diagnosis was confirmed by bronchoscopy and skin biopsy. Computed tomographic features of KS are extremely helpful in guiding the initial management of HIV-infected patients presenting with symptoms of pneumonia.

Mayo Clinic

Sézary syndrome, Kaposi sarcoma and generalized dermatophytosis 15 years after sulfur mustard gas exposure.

Sept 2012

Emadi SN, Babamahmoodi F, Poursaleh Z, Sayad-Noori SS, Soroush MR, Maleki AR, Izadi M, Khodaei-Ardakan MR, Emadi SE.

Source

Chemical Injuries Research Center, Baqiyatallah University of Medical Sciences, Tehran, Iran ; Skin Research Center, Mazandaran University of Medical Sciences, Sari, Iran ; Tehran University of Medical Sciences, Tehran, Iran.

Abstract

BACKGROUND:

The relationship between compromised immune system and the development of malignancy, generalized dermatitis, and infection after sulfur mustard gas exposure has been established.

MAIN OBSERVATION:

We introduce a 58-year-old man with an abrupt, de novo and erythrodermic eruption in 2002 that was previously exposed to sulfur mustard during the Iran - Iraq war in 1987. Six weeks after the onset of diffuse eruption, he developed papules on the glans penis and generalized dermatophytosis. A biopsy of his eruption was consistent with cutaneous T-cell lymphoma/Sézary syndrome. A complete blood count demonstrated leukocytosis, eosinophilia and atypical lymphocytosis. Subsequently, Sézary syndrome was confirmed and T-cell count with increased CD4/CD8 in flow cytometry. The biopsy of his penile papules was consistent with Kaposi's sarcoma.

CONCLUSION:

These findings suggest a causative relationship between sulfur mustard gas exposure, cutaneous T cell lymphoma and immune compromised state with opportunistic infections.

PubMed - Journal of Dermatological Case Reports

miRNAs and usRNAs Discovered in Kaposi's Sarcoma-associated Herpesvirus Virions.

Sept 2012

Lin X, Li X, Liang D, Lan K.

Source

Key Laboratory of Molecular Virology and Immunology, Institut Pasteur of Shanghai, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200025, China.

Abstract

It is widely held that any given virus uses only one type of nucleic acids for genetic information storage. However, this consensus has been challenged a little bit by several recent studies showing that many RNA species are present within a range of DNA viruses that include Kaposi's sarcoma-associated herpesvirus (KSHV). RNAs extracted from purified DNA virus particles exhibit great diversity in terms of length, abundance, temporal expression, cellular localization, and coding capacity during viral infection. In addition to known RNA species, the current study showed that small regulatory RNAs were present in KSHV virion. A large number of viral and cellular miRNAs, as well as unusual small RNAs (usRNAs), were detected in KSHV virion by using deep sequencing. Both viral and host miRNAs detected in small RNAs extracted from KSHV virions were further shown to co-localize with KSHV virion directly by in situ hybridization (ISH)-electron microscopy (EM) (ISH-EM). Some of these miRNAs were differentially present in the host cells and KSHV virions, suggesting that they are not randomly present in KSHV virions. The virional miRNAs could be transported into host cells and they are biologically functional during de novo viral infection. Our study revealed miRNAs and usRNAs as a novel group of component in KSHV virion.

Journal of Virology