Development of Whole-Virus Multiplex Luminex-Based Serological Assays for Diagnosis of Infections with Kaposi's Sarcoma-Associated Herpesvirus/Human Herpesvirus 8 Homologs in Macaques

Ryan, John; Rose, Timothy M.

doi:10.1128/cvi.00673-12

Cited by 9 publications

(15 citation statements)

References 41 publications

(55 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The herpes B virus (BV, Macacine alphaherpesvirus 1) naturally infects macaques, which usually do not develop disease, but the transmission of the virus to other NHPs and humans can induce severe disease Jones-Engel, 2017, 2018). Moreover, infection by the simian immunodeficiency virus (SIV) and simian type D retroviruses (SRV/D) can cause immunodeficiency in NHPs (Schmitz and Korioth-Schmitz, 2013;Daniel et al, 1984;Marx et al, 1984;Stromberg et al, 1984) and SIV transmission from African NHPs to humans gave rise to HIV/AIDS (Sharp and Hahn, 2010). Evidence for SRV/D transmission to humans has also been obtained but has so far not been associated with disease (Lerche et al, 2001).…”

Section: Introductionmentioning

confidence: 99%

Seroprevalence of viral infections in captive rhesus and cynomolgus macaques

2019

View full text Add to dashboard Cite

Abstract. Macaques serve as important animal models for biomedical research. Viral infection of macaques can compromise animal health as well as the results of biomedical research, and infected animals constitute an occupational health risk. Therefore, monitoring macaque colonies for viral infection is an important task. We used a commercial chip-based assay to analyze sera of 231 macaques for the presence of antibody responses against nine animal and human viruses. We report high seroprevalence of cytomegalovirus (CMV), lymphocryptovirus (LCV), rhesus rhadinovirus (RRV) and simian foamy virus (SFV) antibodies in all age groups. In contrast, antibodies against simian retrovirus type D (SRV/D) and simian T cell leukemia virus (STLV) were detected only in 5 % and 10 % of animals, respectively, and were only found in adult or aged animals. Moreover, none of the animals had antibodies against herpes B virus (BV), in keeping with the results of in-house tests previously used for screening. Finally, an increased seroprevalence of measles virus antibodies in animals with extensive exposure to multiple humans for extended periods of time was observed. However, most of these animals were obtained from external sources, and a lack of information on the measles antibody status of the animals at the time of arrival precluded drawing reliable conclusions from the data. In sum, we show, that in the colony studied, CMV, LCV, RRV and SFV infection was ubiquitous and likely acquired early in life while SRV/D and STLV infection was rare and likely acquired during adulthood.

show abstract

Section: Introductionmentioning

confidence: 99%

Seroprevalence of viral infections in captive rhesus and cynomolgus macaques

2019

View full text Add to dashboard Cite

show abstract

“…In the current study, we attempted to transmit RFHV using saliva from naturally infected macaques at the WaNPRC. We previously developed whole-virus multiplex luminex-based serological assays and qPCR assays for diagnosis of RV1 and RV2 rhadinovirus infections in macaques [ 65 ] [ 34 , 51 , 66 ]. We used these assays to screen the WaNPRC colony for seronegative/PCR-negative macaques as transmission recipients and RV1-positive macaques as transmission donors.…”

Section: Introductionmentioning

confidence: 99%

Experimental co-transmission of Simian Immunodeficiency Virus (SIV) and the macaque homologs of the Kaposi Sarcoma-Associated Herpesvirus (KSHV) and Epstein-Barr Virus (EBV)

et al. 2018

Self Cite

View full text Add to dashboard Cite

Macaque RFHV and LCV are close homologs of human KSHV and EBV, respectively. No experimental model of RFHV has been developed due to the lack of a source of culturable infectious virus. Screening of macaques at the Washington National Primate Research Center detected RFHV in saliva of SIV-infected macaques from previous vaccine studies. A pilot experimental infection of two naïve juvenile pig-tailed macaques was initiated by inoculation of saliva from SIV-infected pig-tailed and cynomolgus macaque donors, which contained high levels of DNA (> 106 genomes/ml) of the respective species-specific RFHV strain. Both juvenile recipients developed SIV and RFHV infections with RFHV DNA detected transiently in saliva and/or PBMC around week 16 post-infection. One juvenile macaque was infected with the homologous RFHVMn from whole saliva of a pig-tailed donor, which had been inoculated into the cheek pouch. This animal became immunosuppressed, developing simian AIDS and was euthanized 23 weeks after inoculation. The levels of RFHV DNA in saliva and PBMC remained below the level of detection after week 17, showing no reactivation of the RFHVMn infection during the rapid development of AIDS. The other juvenile macaque was infected with the heterologous RFHVMf from i.v. inoculation of purified virions from saliva of a cynomolgus donor. The juvenile recipient remained immunocompetent, developing high levels of persistent anti-RFHV and -SIV antibodies. After the initial presence of RFHVMf DNA in saliva and PBMC decreased to undetectable levels by week 19, all attempts to reactivate the infection through additional inoculations, experimental infection with purified SRV-2 or SIV, or immunosuppressive treatments with cyclosporine or dexamethasone were unsuccessful. An heterologous LCV transmission was also detected in this recipient, characterized by continual high levels of LCVMf DNA from the cynomolgus donor in both saliva (> 106 genomes/ml) and PBMC (> 104 genomes/million cells), coupled with high levels of anti-LCV antibodies. The macaque was sacrificed 209 weeks after the initial inoculation. Low levels of LCVMf DNA were detected in salivary glands, tonsils and other lymphoid organs, while RFHVMf DNA was below the level of detection. These results show successful co-transmission of RFHV and LCV from saliva and demonstrate differential lytic activation of the different gammaherpesvirus lineages due to presumed differences in biology and tropism and control by the host immune system. Although this initial pilot transmission study utilized only two macaques, it provides the first evidence for experimental transmission of the macaque homolog of KSHV, setting the stage for larger transmission studies to examine the differential activation of rhadinovirus and lymphocryptovirus infections and the pathological effects of immunosuppression.

show abstract

“…Subsequently, M04023 mounted strong long-term immune responses to the virion proteins of both RFHVMf and MfaLCV, indicating successful cross-species infection with the cynomolgus homologs of RFHV and LCV. Unlike many other serological assays for KSHV and EBV, the Luminex assays used in this study detect antibodies to virion proteins, which are generated during primary infections and reactivation of lytic replication and do not target antibodies to specific latency antigens [65]. No RFHV DNA was detected in PBMC or saliva of M04203 after week 19, indicating that the immune system was controlling the RFHVMf infection and suppressing viral reactivation.…”

Section: Discussionmentioning

confidence: 99%

“…Plasma samples were obtained during the biannual health screening of macaques at the WaNPRC and tested with the RV1 and RV2-specific Luminex assays for evidence of RV1 and/or RV2 rhadinovirus infections, which are endemic in the colony [65]. Two juvenile M. nemestrina M04203 (1.0 years) and K04199 (0.5 years) were determined to be naïve for both macaque RV1 and RV2 rhadinovirus infections by Luminex-based serological and qPCR molecular assays.…”

Section: Methodsmentioning

confidence: 99%

Experimental co-transmission of simian immunodeficiency virus (SIV) and the macaque homologs of the Kaposi sarcoma-associated herpesvirus (KSHV) and Epstein-Barr virus (EBV)

Bruce¹,

Barcy²,

Staheli³

et al. 2018

Preprint

Self Cite

View full text Add to dashboard Cite

Macaque RFHV and LCV are close homologs of human KSHV and EBV, respectively. No experimental model of RFHV has been developed due to the lack of a source of culturable infectious virus. Screening of macaques at the Washington National Primate Research Center detected RFHV in saliva of SIV-infected macaques from previous vaccine studies. A pilot experimental infection of two naïve juvenile pig-tailed macaques was initiated by inoculation of saliva from SIV-infected pig-tailed and cynomolgus macaque donors, which contained high levels of DNA of the respective species-specific RFHV strain. Both juvenile recipients developed SIV and RFHV infections with RFHV DNA detected transiently in saliva and/or PBMC around week 16 post-infection. One juvenile macaque was infected with the homologous RFHVMn from whole saliva of a pig-tailed donor, which had been inoculated into the cheek pouch. This animal became immunosuppressed, developing simian AIDS and was euthanized 23 weeks after inoculation. The levels of RFHV DNA in saliva and PBMC remained below the level of detection after week 17, showing no reactivation of the RFHVMn infection during the rapid development of AIDS. The other juvenile macaque was infected with the heterologous RFHVMf from i.v. inoculation of purified virions from saliva of a cynomolgus donor. The juvenile recipient remained immunocompetent, developing high levels of persistent anti-RFHV and -SIV antibodies. After the initial presence of RFHVMf DNA in saliva and PBMC decreased to undetectable levels by week 19, all attempts to reactivate the infection through additional inoculations, experimental infection with purified SRV-2 or SIV, or immunosuppressive treatments with cyclosporine or dexamethasone were unsuccessful. An heterologous LCV transmission was also detected in this recipient, characterized by continual high levels of LCVMf DNA from the cynomolgus donor in both saliva and PBMC, coupled with high levels of anti-LCV antibodies. The macaque was sacrificed 209 weeks after the initial inoculation. Low levels of LCVMf DNA were detected in salivary glands, tonsils and other lymphoid organs, while RFHVMf DNA was below the level of detection. These results show successful co-transmission of RFHV and LCV from saliva and demonstrate differential lytic activation of the different gammaherpesvirus lineages due to presumed differences in biology and tropism and control by the host immune system. Although this initial pilot transmission study utilized only two macaques, it provides the first evidence for experimental transmission of the macaque homolog of KSHV, setting the stage for larger transmission studies to examine the differential activation of rhadinovirus and lymphocryptovirus infections and the pathological effects of immunosuppression.

show abstract

Development of Whole-Virus Multiplex Luminex-Based Serological Assays for Diagnosis of Infections with Kaposi's Sarcoma-Associated Herpesvirus/Human Herpesvirus 8 Homologs in Macaques

Cited by 9 publications

References 41 publications

Seroprevalence of viral infections in captive rhesus and cynomolgus macaques

Seroprevalence of viral infections in captive rhesus and cynomolgus macaques

Experimental co-transmission of Simian Immunodeficiency Virus (SIV) and the macaque homologs of the Kaposi Sarcoma-Associated Herpesvirus (KSHV) and Epstein-Barr Virus (EBV)

Experimental co-transmission of simian immunodeficiency virus (SIV) and the macaque homologs of the Kaposi sarcoma-associated herpesvirus (KSHV) and Epstein-Barr virus (EBV)

Contact Info

Product

Resources

About