comparison of vaccination with rhesus cmv (rhcmv) soluble gb with a rhcmv replication-defective virus deleted for mhc class i immune evasion genes in a rhcmv challenge model. | a human cytomegalovirus (hcmv) vaccine to prevent infection and/or reduce disease associated with congenital infection or visceral disease in transplant recipients is a high priority, but has remained elusive. we created a disabled infectious single cycle rhesus cmv (rhcmv) deleted for glycoprotein l (gl) and the mhc class i immune evasion genes rh178 and rh182-189, and restored its epithelial cell tropism by inserting the rh128-131a genes. the resulting virus, rhcmvrδgl/178/182-189, was used to ... | 2019 | 30522906 |
cmv primes functional alternative signaling in adaptive δg nk cells but is subverted by lentivirus infection in rhesus macaques. | despite burgeoning evidence demonstrating the adaptive properties of natural killer (nk) cells, mechanistic data explaining these phenomena are lacking. following antibody sensitization, nk cells lacking the fc receptor (fcr) signaling chain (δg) acquire adaptive features, including robust proliferation, multifunctionality, rapid killing, and mobilization to sites of virus exposure. using the rhesus macaque model, we demonstrate the systemic distribution of δg nk cells expressing memory features ... | 2018 | 30517864 |
identification and functional characterization of a novel fc gamma-binding glycoprotein in rhesus cytomegalovirus. | receptors recognizing the fc part of immunoglobulin g (fcγrs) are key determinants in antibody-mediated immune responses. members of the herpesviridae interfere with this immune regulatory network by expressing viral fcγrs (vfcγrs). human cytomegalovirus (hcmv) encodes four distinct vfcγrs that differ with respect to their igg subtype specificity and their impact on antibody-mediated immune function in vitro the impact of vfcγrs on hcmv pathogenesis and immunomodulation in vivo is not known. the ... | 2019 | 30487278 |
natural history of postnatal rhesus cytomegalovirus shedding by dams and acquisition by infant rhesus monkeys. | human infants frequently acquire human cytomegalovirus (hcmv) through breastfeeding, resulting in persistent high-level viral shedding in saliva and urine and infectivity to others, including pregnant women. thus, vaccination to interrupt postnatal hcmv transmission is an attractive strategy to prevent hcmv spread and congenital infection. rhesus cmv (rhcmv) in nonhuman primates is a valuable model for the study of immune strategies to prevent cmv transmission. although rhesus monkeys typically ... | 2018 | 30356332 |
long-term safety outcome of systemic immunosuppression in pig-to-nonhuman primate corneal xenotransplantation. | safety concerns exist for corneal recipients under immunosuppression. we report long-term safety results of porcine corneal xenotransplantation under immunosuppression in nonhuman primates. | 2018 | 30264877 |
early antiretroviral therapy limits siv reservoir establishment to delay or prevent post-treatment viral rebound. | prophylactic vaccination of rhesus macaques with rhesus cytomegalovirus (rhcmv) vectors expressing simian immunodeficiency virus (siv) antigens (rhcmv/siv) elicits immune responses that stringently control highly pathogenic siv infection, with subsequent apparent clearance of the infection, in ~50% of vaccinees. in contrast, here, we show that therapeutic rhcmv/siv vaccination of rhesus macaques previously infected with siv and given continuous combination antiretroviral therapy (cart) beginning ... | 2018 | 30082858 |
interleukin-15 response signature predicts rhcmv/siv vaccine efficacy. | simian immunodeficiency virus (siv) challenge of rhesus macaques (rms) vaccinated with strain 68-1 rhesus cytomegalovirus (rhcmv) vectors expressing siv proteins (rhcmv/siv) results in a binary outcome: stringent control and subsequent clearance of highly pathogenic siv in ~55% of vaccinated rms with no protection in the remaining 45%. although previous work indicates that unconventionally restricted, siv-specific, effector-memory (em)-biased cd8+ t cell responses are necessary for efficacy, the ... | 2021 | 34228762 |
cytomegaloviral determinants of cd8+ t cell programming and rhcmv/siv vaccine efficacy. | simian immunodeficiency virus (siv) insert-expressing, 68-1 rhesus cytomegalovirus (rhcmv/siv) vectors elicit major histocompatibility complex e (mhc-e)- and mhc-ii-restricted, siv-specific cd8+ t cell responses, but the basis of these unconventional responses and their contribution to demonstrated vaccine efficacy against siv challenge in the rhesus monkeys (rms) have not been characterized. we show that these unconventional responses resulted from a chance genetic rearrangement in 68-1 rhcmv t ... | 2021 | 33766849 |
in vitro and in vivo characterization of a recombinant rhesus cytomegalovirus containing a complete genome. | cytomegaloviruses (cmvs) are highly adapted to their host species resulting in strict species specificity. hence, in vivo examination of all aspects of cmv biology employs animal models using host-specific cmvs. infection of rhesus macaques (rm) with rhesus cmv (rhcmv) has been established as a representative model for infection of humans with hcmv due to the close evolutionary relationships of both host and virus. however, the only available rhcmv clone that permits genetic modifications is bas ... | 2020 | 33232376 |