Lytic growth of Kaposi's sarcoma–associated herpesvirus (human herpesvirus 8) in culture

Abstract

Kaposi's sarcoma (KS) is the leading neoplasm of AIDS patients, and HIV infection is known to be a major risk factor for its development. However, KS can occur in the absence of HIV infection and the risk of KS development varies widely even among HIV-infected patients, with homosexual men with AIDS being 20 times more likely to develop KS than AIDS-afflicted children or hemophiliacs. These and other data strongly suggest that a sexually transmitted agent or co-factor may be involved in KS pathogenesis. Recently, DNA sequences corresponding to the genome of a novel member of the herpesvirus family have been identified within AIDS-KS biopsies, and several reports indicate that these sequences are also present in all forms of HIV-negative KS. These and other findings suggest this new agent, referred to as KS-associated herpesvirus (KSHV) or human herpesvirus 8 (HHV8), as a candidate for the putative etiologic cofactor. However, the role of this agent in KS remains hotly debated. Further progress in understanding its biology has been severely hampered by the lack of a cell culture system for virus growth. Here we report the development of a system for the lytic growth of this virus in a latently infected B cell line and present the first ultrastructural visualization of the virus. This system will facilitate the detailed study of the molecular biology of viral replication, the testing of antiviral drugs and the development of diagnostic tests for viral infection.

Epidemiology of Kaposi's sarcoma in the Nordic countries before the AIDS epidemic

“…DNA sequences from a Herpesvirus have recently been detected in both AIDSrelated and classical KS lesions (Su et al, 1995;Chang et al, 1994) and culturing of the virus has been reported (Renne et al, 1996). If involved in the aetiology of KS, differences in the prevalence of the virus with respect to time and place or in cofactors determining disease progression offer a plausible explanation for the observed geographic variation and the observed increase in KS incidence.…”

Lymphoma cell lines: in vitro models for the study of HHV-8+ primary effusion lymphomas (body cavity-based lymphomas)

“…15 Strong evidence that the infection of PEL cell lines with HHV-8 represents a true latent infection rather than an aberrant or 'dead end' infection came from experiments showing that a switch to productive (lytic) replication was induced in response to appropriate stimuli. 28 Indeed, BCBL-1 (HHV-8+ EBV-neg) exposed to phorbol ester TPA switched to productive (lytic) HHV-8 replication, whereas TPA did not induce this switch in BCBL-2 (HHV-8+ EBV+) raising the possibility that EBV may somehow interfere with HHV-8 induction. 28 Six PEL cell lines are co-infected with EBV, showing a monoclonal pattern of EBV infection (Figure 4b), whereas the remaining five cell lines are EBV-negative (Table 3, Figure 3) suggesting that EBV is not an absolute requirement for the establishment of the cell lines.…”

“…28 Indeed, BCBL-1 (HHV-8+ EBV-neg) exposed to phorbol ester TPA switched to productive (lytic) HHV-8 replication, whereas TPA did not induce this switch in BCBL-2 (HHV-8+ EBV+) raising the possibility that EBV may somehow interfere with HHV-8 induction. 28 Six PEL cell lines are co-infected with EBV, showing a monoclonal pattern of EBV infection (Figure 4b), whereas the remaining five cell lines are EBV-negative (Table 3, Figure 3) suggesting that EBV is not an absolute requirement for the establishment of the cell lines. 8 Furthermore, most EBV+ cell lines display a restricted EBV antigen profile being negative for EBNA-2 and LMP-1 expression, two EBV-encoded transforming antigens.…”

Cellular defence or viral assist: the dilemma of HDAC6

“…This raises the possibility that inhibition of HDACs may reactivate latent proviruses. Indeed, HDAC6 inhibitors, as well as other HDACs, are subsequently found to reactivate HIV [141][142][143][144], EpsteinBarr virus [145][146][147], Kaposi's sarcoma-associated herpesvirus (KSHV) [148,149] and feline immunodeficiency virus [150].…”