Kaposi's sarcoma-associated herpesvirus/human herpesvirus 8 infection in reactive lymphoid tissues: a model for KSHV/HHV-8-related lymphomas?
We set out to analyze the presence of Kaposi's sarcoma-associated herpesvirus (KSHV)/human herpesvirus 8 (HHV-8) in different neoplasms occurring in East Africa, a region characterized by a high KSHV/HHV-8 seroprevalence rate and endemic Kaposi's sarcoma (KS). Our results suggest that, in endemic regions of Africa, KSHV/HHV-8 is predominantly associated with KS, independently of HIV status. During the course of this study, other important information came to light. We found the presence of KSHV/HHV-8 in 2 cases of lymph nodes partially involved by Burkitt's lymphoma and KS and in 1 case of multicentric Castleman disease. Our immunophenotypic and molecular data seem to suggest 2 different mechanisms of viral infection are at work in lymphoid cells. On one hand, when B cells show a latent phase infection with KSHV/HHV-8, after the germinal center reaction, naive B cells become resting memory B cells, similarly to Epstein-Barr virus-infected B cells. On the other hand, when lytic genes such as vIL6 are expressed in naive B cells, they may be driven to differentiate into plasmablasts without undergoing germinal center reaction. Interestingly, among KSHV/HHV-8-positive cases, in those in which there was also lymphoma, the neoplastic cells were negative for KSHV/HHV-8. This further confirms that KSHV/HHV-8 is involved in the neoplastic transformation of only certain types of lymphoma, probably in relation to their precursor infected cell. In conclusion, the maturation stage of KSHV/HHV-8-positive B cells as well as the type of viral infection may well determine the morphological, phenotypic, and clinical characteristics of KSHV/HHV-8-associated lymphomas.
Lazzi
Stefano
S
Department of Human Pathology and Oncology, University of Siena, 53100, Italy.
Bellan
Cristiana
C
Amato
Teresa
T
Palummo
Nazzareno
N
Cardone
Concetta
C
D'Amuri
Alessandro
A
De Luca
Fabio
F
Beyanga
Medard
M
Facchetti
Fabio
F
Tosi
Piero
P
Leoncini
Lorenzo
L
D000328:Adult; D000956:Antigens, Viral; D001402:B-Lymphocytes / Q000473:pathology / Q000821:virology; D002051:Burkitt Lymphoma / Q000473:pathology / Q000821:virology; D005871:Castleman Disease / Q000473:pathology / Q000821:virology; D002471:Cell Transformation, Neoplastic; D002648:Child; D004279:DNA, Viral / Q000032:analysis; D005260:Female; D018858:Germinal Center / Q000473:pathology / Q000821:virology*; D006678:HIV / Q000235:genetics / Q000302:isolation & purification; D004854:Herpesvirus 4, Human / Q000235:genetics / Q000302:isolation & purification; D019288:Herpesvirus 8, Human / Q000235:genetics / Q000276:immunology / Q000302:isolation & purification*; D006801:Humans; D008223:Lymphoma / Q000473:pathology / Q000821:virology*; D008297:Male; D008875:Middle Aged; D009687:Nuclear Proteins; D012367:RNA, Viral / Q000032:analysis; D012189:Retrospective Studies; D012514:Sarcoma, Kaposi / Q000473:pathology / Q000821:virology*
D000956:Antigens, Viral; D004279:DNA, Viral; D009687:Nuclear Proteins; D012367:RNA, Viral; C109540:latency-associated nuclear antigen