Vertical transmission of Kaposi's sarcoma-associated herpesvirus

Mantina, Hamakwa; Kankasa, Chipepo; Klaskala, Winslow; Brayfield, Brad; Campbell, James J.; Du, Quijiang; Bhat, Ganapati; Kasolo, Francis; Mitchell, Charles D.; Wood, Charles

doi:10.1002/ijc.1529

Cited by 83 publications

(54 citation statements)

References 25 publications

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“…DNA was extracted from mice tissue samples using the Puregene Genomic DNA Purification Kit (Qiagen) according to the manufacturer's protocol. DNA was analyzed for KSHV DNA by PCR of the orf26 gene using a previously described nested PCR protocol (24).…”

Section: Methodsmentioning

confidence: 99%

Humanized-BLT mouse model of Kaposi’s sarcoma-associated herpesvirus infection

Wang

Kang

Kumar

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

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Lack of an effective small-animal model to study the Kaposi's sarcoma-associated herpesvirus (KSHV) infection in vivo has hampered studies on the pathogenesis and transmission of KSHV. The objective of our study was to determine whether the humanized BLT (bone marrow, liver, and thymus) mouse (hu-BLT) model generated from NOD/SCID/IL2rγ mice can be a useful model for studying KSHV infection. We have tested KSHV infection of hu-BLT mice via various routes of infection, including oral and intravaginal routes, to mimic natural routes of transmission, with recombinant KSHV over a 1-or 3-mo period. Infection was determined by measuring viral DNA, latent and lytic viral transcripts and antigens in various tissues by PCR, in situ hybridization, and immunohistochemical staining. KSHV DNA, as well as both latent and lytic viral transcripts and proteins, were detected in various tissues, via various routes of infection. Using double-labeled immune-fluorescence confocal microscopy, we found that KSHV can establish infection in human B cells and macrophages. Our results demonstrate that KSHV can establish a robust infection in the hu-BLT mice, via different routes of infection, including the oral mucosa which is the most common natural route of infection. This hu-BLT mouse not only will be a useful model for studying the pathogenesis of KSHV in vivo but can potentially be used to study the routes and spread of viral infection in the infected host. T he Kaposi's sarcoma (KS)-associated herpesvirus (KSHV), also known as the human herpesvirus 8, was first identified from KS tissues in 1994 (1). It is the etiologic agent for KS and is also associated with primary effusion lymphoma (PEL) and multicentric Castleman's disease (2). More recently it was also found to be associated with KSHV-associated inflammatory cytokine syndrome (3). Although substantial progress has been made in characterizing the virus, there are still many unanswered questions such as how KSHV infection can lead to disease manifestation and whether latent or lytic induction of KSHV are associated with malignancies. One of the reasons is a lack of a good small-animal model to study KSHV infection in vivo, which has hampered studies on how KSHV infects, spreads, and how it interacts with the host and ultimately leads to disease pathogenesis. Moreover, currently there is no vaccine against KSHV infection, and there is need for an effective animal model to evaluate the efficacy of vaccines if they are developed and for the testing of antiviral regimens.An ideal model should have relatively short generation time, reproduce rapidly, be inexpensive to maintain and house, and be easy to manipulate. An example is a rodent model that can be infected by KSHV effectively. Several small-rodent models have been tested for KSHV infection. The models include transplantation with both human KSHV-infected B lymphoma cells and primary human peripheral blood mononuclear cells in the SCID mouse (4), injection of KSHV into the human skin engrafted or the transplant of the SCID mice...

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Section: Methodsmentioning

confidence: 99%

Humanized-BLT mouse model of Kaposi’s sarcoma-associated herpesvirus infection

Wang

Kang

Kumar

et al. 2014

Proc. Natl. Acad. Sci. U.S.A.

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“…For example, 83% of Zambian infants were KSHV seropositive if born to a mother who was also seropositive; however, only 3% of the infants had detectable KSHV DNA in their PBMCs (322). Frequent studies have demonstrated a loss of KSHV seropositivity in children after infancy.…”

Section: Endemic (African) Ksmentioning

confidence: 99%

Molecular Genetics of Kaposi's Sarcoma-Associated Herpesvirus (Human Herpesvirus 8) Epidemiology and Pathogenesis

Dourmishev

Palmeri

et al. 2003

Microbiol Mol Biol Rev

309

367

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Kaposi's sarcoma had been recognized as unique human cancer for a century before it manifested as an AIDS-defining illness with a suspected infectious etiology. The discovery of Kaposi's sarcoma-associated herpesvirus (KSHV), also known as human herpesvirus-8, in 1994 by using representational difference analysis, a subtractive method previously employed for cloning differences in human genomic DNA, was a fitting harbinger for the powerful bioinformatic approaches since employed to understand its pathogenesis in KS. Indeed, the discovery of KSHV was rapidly followed by publication of its complete sequence, which revealed that the virus had coopted a wide armamentarium of human genes; in the short time since then, the functions of many of these viral gene variants in cell growth control, signaling apoptosis, angiogenesis, and immunomodulation have been characterized. This critical literature review explores the pathogenic potential of these genes within the framework of current knowledge of the basic herpesvirology of KSHV, including the relationships between viral genotypic variation and the four clinicoepidemiologic forms of Kaposi's sarcoma, current viral detection methods and their utility, primary infection by KSHV, tissue culture and animal models of latent- and lytic-cycle gene expression and pathogenesis, and viral reactivation from latency. Recent advances in models of de novo endothelial infection, microarray analyses of the host response to infection, receptor identification, and cloning of full-length, infectious KSHV genomic DNA promise to reveal key molecular mechanisms of the candidate pathogeneic genes when expressed in the context of viral infection

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“…In this case, tumor development is associated with immunosuppressive therapy (35). Vertical KSHV transmission was demonstrated by Mantina et al (36) who found viral DNA in two neonates; moreover, the authors emphasize that it may not be possible to determine if infection occurred in utero or intrapartum, but postnatal infection was ruled out due to the impossibility to detect DNA during the immediate postnatal period.…”

Section: Discussionmentioning

confidence: 88%

Kaposi's sarcoma-associated herpesvirus infection and Kaposi's sarcoma in Brazil

Silva

Oliveira

Borges

et al. 2006

Braz J Med Biol Res

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Kaposi's sarcoma (KS) became a critical health issue with the emergence of acquired immunodeficiency syndrome (AIDS) in the 1980s. Four clinical-epidemiological forms of KS have been described: classical KS, endemic KS, iatrogenic KS, and AIDS-associated KS. In 1994, Kaposi's sarcoma-associated herpesvirus (KSHV) or human herpesvirus type 8 was identified by Chang and colleagues, and has been detected worldwide at frequencies ranging from 80 to 100%. The aim of the present study was to evaluate the frequency of KSHV infection in KS lesions from HIV-positive and HIV-negative patients in Brazil, as well as to review the current knowledge about KS transmission and detection. For these purposes, DNA from 51 cases of KS was assessed by PCR: 20 (39.2%) cases of classical KS, 29 (56.9%) of AIDS-associated KS and 2 (3.9%) of iatrogenic KS. Most patients were males (7.5:1, M/F), and mean age was 47.9 years (SD = ± 18.7 years). As expected, HIV-positive KS patients were younger than patients with classical KS. On the other hand, patients with AIDS-associated KS have early lesions (patch and plaque) compared to classical KS patients (predominantly nodular lesions). This is assumed to be the result of the early diagnose of KS in the HIVpositive setting. KSHV infection was detected by PCR in almost all cases (48/51; 94.1%), irrespectively of the clinical-epidemiological form of KS. These results show that KSHV is associated with all forms of KS in Brazilian patients, a fact that supports the role of this virus in KS pathogenesis. Correspondence

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Vertical transmission of Kaposi's sarcoma-associated herpesvirus

Cited by 83 publications

References 25 publications

Humanized-BLT mouse model of Kaposi’s sarcoma-associated herpesvirus infection

Humanized-BLT mouse model of Kaposi’s sarcoma-associated herpesvirus infection

Molecular Genetics of Kaposi's Sarcoma-Associated Herpesvirus (Human Herpesvirus 8) Epidemiology and Pathogenesis

Kaposi's sarcoma-associated herpesvirus infection and Kaposi's sarcoma in Brazil

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