DeNovo Infection with Rhesus Monkey Rhadinovirus Leads to theAccumulation of Multiple Intranuclear Capsid Species during LyticReplication but Favors the Release of Genome-ContainingVirions

O’Connor, Christine M.; Damania, Blossom; Kedes, Dean H.

doi:10.1128/jvi.77.24.13439-13447.2003

Cited by 19 publications

(20 citation statements)

References 56 publications

(61 reference statements)

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“…However, this could seem unlikely given the tight packing of DNA which requires the entire internal content of the capsid (5). B capsids could also be released from dying cells or particles that lack DNA could occasionally bud, as previously observed for KSHV and RRV (39,40). This would explain the detection of the BoHV-4 pORF17.5 in our samples (see Fig.…”

Section: Discussionsupporting

confidence: 63%

Proteomic Characterization of Bovine Herpesvirus 4 Extracellular Virions

Lété

Palmeira

Leroy

et al. 2012

J Virol

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cGammaherpesviruses are important pathogens in human and animal populations. During early events of infection, these viruses manipulate preexisting host cell signaling pathways to allow successful infection. The different proteins that compose viral particles are therefore likely to have critical functions not only in viral structures and in entry into target cell but also in evasion of the host's antiviral response. In this study, we analyzed the protein composition of bovine herpesvirus 4 (BoHV-4), a close relative of the human Kaposi's sarcoma-associated herpesvirus. Using mass spectrometry-based approaches, we identified 37 viral proteins associated with extracellular virions, among which 24 were resistant to proteinase K treatment of intact virions. Analysis of proteins associated with purified capsid-tegument preparations allowed us to define protein localization. In parallel, in order to identify some previously undefined open reading frames, we mapped peptides detected in whole virion lysates onto the six frames of the BoHV-4 genome to generate a proteogenomic map of BoHV-4 virions. Furthermore, we detected important glycosylation of three envelope proteins: gB, gH, and gp180. Finally, we identified 38 host proteins associated with BoHV-4 virions; 15 of these proteins were resistant to proteinase K treatment of intact virions. Many of these have important functions in different cellular pathways involved in virus infection. This study extends our knowledge of gammaherpesvirus virions composition and provides new insights for understanding the life cycle of these viruses.

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Section: Discussionsupporting

confidence: 63%

Proteomic Characterization of Bovine Herpesvirus 4 Extracellular Virions

Lété

Palmeira

Leroy

et al. 2012

J Virol

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“…In contrast, rhesus monkey rhadinovirus (RRV), a nonhuman primate gamma-2 herpesvirus with high levels of homology to KSHV, grows to high titer in culture (2,33,47,64). We have previously characterized the capsids of both KSHV and RRV (30,33,56,64). In these studies, we found that the three-dimensional capsid structures and protein homolog compositions were strikingly similar (33, 64).…”

mentioning

confidence: 95%

“…Unfortunately, KSHV grows to low titer in culture, making detailed structural and compositional studies of highly purified particles particularly challenging (4,65). In contrast, rhesus monkey rhadinovirus (RRV), a nonhuman primate gamma-2 herpesvirus with high levels of homology to KSHV, grows to high titer in culture (2,33,47,64). We have previously characterized the capsids of both KSHV and RRV (30,33,56,64).…”

mentioning

confidence: 99%

Mass Spectrometric Analyses of Purified Rhesus Monkey Rhadinovirus Reveal 33 Virion-Associated Proteins

O’Connor

Kedes

2006

J Virol

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The repertoire of proteins that comprise intact gammaherpesviruses, including the human pathogen Kaposi's sarcoma-associated herpesvirus (KSHV), is likely to have critical functions not only in viral structure and assembly but also in the early stages of infection and evasion of the host's rapidly deployed antiviral defenses. To develop a better understanding of these proteins, we analyzed the composition of rhesus monkey rhadinovirus (RRV), a close phylogenetic relative of KSHV. Unlike KSHV, RRV replicates to high titer in cell culture and thus serves as an effective model for studying primate gammaherpesvirus structure and virion proteomics. We employed two complementary mass spectrometric approaches and found that RRV contains at least 33 distinct virally encoded proteins. We have assigned 7 of these proteins to the capsid, 17 to the tegument, and 9 to the envelope. Of the five gammaherpesvirus-specific tegument proteins, three have no known function. We also found three proteins not previously associated with a purified herpesvirus and an additional seven that represent new findings for a member of the gamma-2 herpesviruses. Detergent extraction resulted in particles that contained six distinct tegument proteins in addition to the expected capsid structural proteins, suggesting that this subset of tegument components may interact more directly with or with higher affinity for the underlying capsid and, in turn, may play a role in assembly or transport of viral or subviral particles during entry or egress.Kaposi's sarcoma remains the most common AIDS-related malignancy worldwide, and its causative agent is Kaposi's sarcoma-associated herpesvirus (KSHV), a member of the gamma subfamily of herpesviruses (7, 10). Unfortunately, KSHV grows to low titer in culture, making detailed structural and compositional studies of highly purified particles particularly challenging (4, 65). In contrast, rhesus monkey rhadinovirus (RRV), a nonhuman primate gamma-2 herpesvirus with high levels of homology to KSHV, grows to high titer in culture (2,33,47,64). We have previously characterized the capsids of both KSHV and RRV (30,33,56,64). In these studies, we found that the three-dimensional capsid structures and protein homolog compositions were strikingly similar (33, 64). Both KSHV and RRV exhibit structural features similar to those of other herpesviruses, including an icosahedral capsid (30,56,62) enclosing the viral genome, a proteinaceous tegument, and an envelope (36,44,59) decorated with glycoprotein spikes that facilitate virion-host cell interactions (1,8,9,22,68). These findings, coupled with the high yields of RRV in culture, have made RRV an attractive model system for the study of KSHV structure and assembly (2,30,33,47,64).Alpha-and betaherpesvirus studies provided the basis for early classification schemes for structural components of gammaherpesviruses. However, many structural proteins of the gamma subfamily demonstrate sufficient amino acid sequence divergence from alpha-and betaherpesviruses to suggest that ...

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“…First, the RRV life cycle can be modeled in vivo, in rhesus macaques. Second, RhF support 100% lytic replication of RRV and allows for the production of high titers of virus (ϳ10 6 PFU/ml) (58). Our group has demonstrated that the transcription program of RRV is similar to that of KSHV (17,25).…”

mentioning

confidence: 97%