Supplementary Table from CDK2 Inhibition Enhances Antitumor Immunity by Increasing IFN Response to Endogenous Retroviruses
Yu ChenQiaomei CaiChaohu PanWancheng LiuLili LiJunxiao LiuMeiling GaoXiaorong LiLiguo WangYu RaoHeng YangGenhong Cheng
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Supplementary Table from CDK2 Inhibition Enhances Antitumor Immunity by Increasing IFN Response to Endogenous RetrovirusesKeywords:
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Vaccine/challenge experiments that utilize live attenuated strains of simian immunodeficiency virus (SIV) in monkeys may be useful for elucidating what is needed from a vaccine in order to achieve protective immunity. Derivatives of SIVmac239 and SIVmac239Δnef were constructed in which env sequences were replaced with those of the heterologous strain E543; these were then used in vaccine/challenge experiments. When challenge occurred at 22 weeks, 10 of 12 monkeys exhibited apparent sterilizing immunity despite a mismatch of Env sequences, compared to 12 of 12 monkeys with apparent sterilizing immunity when challenge virus was matched in its Env sequence. However, when challenge occurred at 6 weeks, 6 of 6 SIV239Δnef-immunized monkeys became superinfected by challenge virus mismatched in its Env sequence (SIV239/EnvE543). These results contrast markedly not only with the results of the week 22 challenge but also with the sterilizing immunity observed in 5 of 5 SIV239Δnef-immunized rhesus monkeys challenged at 5 weeks with SIV239, i.e., with no mismatch of Env sequences. We conclude from these studies that a mismatch of Env sequences in the challenge virus can have a dramatic effect on the extent of apparent sterilizing immunity when challenge occurs relatively early, 5 to 6 weeks after the nef-deleted SIV administration. However, by 22 weeks, mismatch of Env sequences has little or no influence on the degree of protection against challenge virus. Our findings suggest that anti-Env immune responses are a key component of the protective immunity elicited by live attenuated, nef-deleted SIV.
Simian immunodeficiency virus
Attenuated vaccine
Heterologous
Simian
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ABSTRACT Recent DNA sequence analysis indicates that rhesus rhadinovirus (RRV) is a member of the lymphotropic gamma-2 herpesvirus family. To determine if RRV is lymphotropic, peripheral blood mononuclear cells from naturally infected monkeys were separated by immunomagnetic bead depletion and analyzed for the presence of RRV by virus isolation and nested PCR. The recovery and consistent detection of RRV in the CD20 + -enriched fraction clearly demonstrates that B lymphocytes are a major site of virus persistence.
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Rhesus monkey rhadinovirus (RRV) is one of the closest phylogenetic relatives to the human pathogen Kaposi's sarcoma-associated herpesvirus (KSHV), yet it has the distinct experimental advantage of entering efficiently into lytic replication and growing to high titers in culture. RRV therefore holds promise as a potentially attractive model with which to study gammaherpesvirus structure and assembly. We have isolated RRV capsids, determined their molecular composition, and identified the genes encoding five of the main capsid structural proteins. Our data indicate that, as with other herpesviruses, lytic infection with RRV leads to the synthesis of three distinct intranuclear capsid species. However, in contrast to the inefficiency of KSHV maturation following reactivation from latently infected B-cell lines (K. Nealon, W. W. Newcomb, T. R. Pray, C. S. Craik, J. C. Brown, and D. H. Kedes, J. Virol. 75:2866-2878, 2001), de novo infection of immortalized rhesus fibroblasts with RRV results in the release of high levels of infectious virions with genome-containing C capsids at their center. Together, our findings argue for the use of RRV as a powerful model with which to study the structure and assembly of gammaherpesviruses and, specifically, the human rhadinovirus,KSHV.
Lytic cycle
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Aedes albopictus
Cytopathic effect
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Pseudorabies
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Monocyte
Albendazole
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Summary Ten replication-competent endogenous avian leukosis viruses (ALVs) with subgroup E specificity were isolated from six commercial chicken lines of mixed breed. All the ALVs isolated belonged to a variant class of endogenous viruses with a major group-specific antigen, p27, identical in size to that of exogenous viruses and different from the p27° of endogenous viruses isolated from White Leghorn chickens. It was possible to infect chickens exogenously with endogenous viruses (containing p27) and with Rous-associated virus type 0 (containing p27°) but infection was non-productive. Congenital transmission and shedding did not occur in chickens infected with endogenous viruses containing p27° or in chickens infected with endogenous viruses containing p27. Restriction of endogenous virus replication in some tissues (heart, spleen and meconia) of viraemic chickens was observed suggesting that exogenous infection of chickens with endogenous viruses differs from an infection with exogenous ALVs.
Endogenous retrovirus
Rous sarcoma virus
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Strain (injury)
Medical microbiology
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The ganglia of rabbits infected with a relatively benign strain of herpesvirus (E-43) and challenged with either of two virulent neurotrophic strains (MP or McKrae) were found to be colonized only by the initial benign infecting strain. Primary infection with the E-43 strain resulted in milder disease when the animals were infected with MP or McKrae strains and also prevented colonization of the ganglion by these strains. Neutralization with anti-glycoprotein C, plaque morphology, cytopathic effects, reconstruction experiments, and restriction endonuclease analysis indicated that the virus recovered from the ganglion was the initial infecting E-43 strain; no traces of the challenging MP and McKrae strains were found. The challenging McKrae strain was shed for several weeks in a few animals, but the virus isolated from the trigeminal ganglia of these animals was the primary infecting E-43 strain. These results suggest that initial infection with a relatively benign strain of herpesvirus may prevent superinfection of the ganglion (but not necessarily the end organ) by highly virulent herpes simplex virus strains and could have significant implications in the consideration of immunization against this disease in humans.
Superinfection
Strain (injury)
Trigeminal ganglion
Simplexvirus
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It was found that in two dioecious species, the carob (Ceratonia siliqua) and the date palm (Phoenix dactylifera) growing in their natural Mediterrancan habitat, the female partner invariably manifested higher endogenous GN-like activity. While this trend was consistent, marked seasonal fluctuations in both free and glycosidic bound-GN were observedhigher levels being associated with essentially vegetative spring growth and the converse associated with anthesis. It is postulated that while a clear correlation exists between female growth and high GN activity in these species, the switch from vegetative to generative growth in both the male and female may be associated with a lower relative proportion of endogenous GN in a specific multi-hormonal complex presumably required for flower induction.
Undergrowth
Gibberellic acid
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