Use of specific‐pathogen‐free (SPF) rhesus macaques to better model oral pediatric cytomegalovirus infection

Pena, Myra Grace dela; Strelow, Lisa; Barry, Peter A.; Abel, Kristina

doi:10.1111/j.1600-0684.2012.00541.x

Cited by 13 publications

(10 citation statements)

References 22 publications

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“…Yet, congenital virus transmission can be modeled using both guinea pigs and nonhuman primate models [7,24]. In particular, rhesus macaques and their corresponding endogenous rhesus CMV (RhCMV) are a highlyrelevant model for understanding adult/fetal HCMV pathogenesis [25,26] and congenital infection [9,27], as the physiology/immunology of rhesus monkey pregnancy is highly analogous to humans [25], there is extensive protein homology between RhCMV and HCMV [28], and certain mechanisms of viral immune evasion are conserved between these viruses [29,30]. Previously, our group demonstrated that the depletion of CD4 + T cells followed by intravenous RhCMV inoculation of seronegative pregnant monkeys resulted in consistent RhCMV congenital infection and a high rate of fetal loss [24].…”

Section: Introductionmentioning

confidence: 99%

Intrahost cytomegalovirus population genetics following antibody pretreatment in a monkey model of congenital transmission

et al. 2020

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Human cytomegalovirus (HCMV) infection is the leading non-genetic cause of congenital birth defects worldwide. While several studies have addressed the genetic composition of viral populations in newborns diagnosed with HCMV, little is known regarding mother-tochild viral transmission dynamics and how therapeutic interventions may impact within-host viral populations. Here, we investigate how preexisting CMV-specific antibodies shape the maternal viral population and intrauterine virus transmission. Specifically, we characterize the genetic composition of CMV populations in a monkey model of congenital CMV infection to examine the effects of passively-infused hyperimmune globulin (HIG) on viral population genetics in both maternal and fetal compartments. In this study, 11 seronegative, pregnant monkeys were challenged with rhesus CMV (RhCMV), including a group pretreated with a standard potency HIG preparation (n = 3), a group pretreated with a high-neutralizing potency HIG preparation (n = 3), and an untreated control group (n = 5). Targeted amplicon deep sequencing of RhCMV glycoprotein B and L genes revealed that one of the three strains present in the viral inoculum (UCD52) dominated maternal and fetal viral populations. We identified minor haplotypes of this strain and characterized their dynamics. Many of the identified haplotypes were consistently detected at multiple timepoints within sampled maternal tissues, as well as across tissue compartments, indicating haplotype persistence over time and transmission between maternal compartments. However, haplotype numbers and diversity levels were not appreciably different between control, standard-potency, and high-potency pretreatment groups. We found that while the presence of maternal antibodies reduced viral load and congenital infection, it had no apparent impact on intrahost viral genetic diversity at the investigated loci. Interestingly, some minor haplotypes present in fetal and maternal-fetal interface tissues were also identified as minor haplotypes in

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Section: Introductionmentioning

confidence: 99%

Intrahost cytomegalovirus population genetics following antibody pretreatment in a monkey model of congenital transmission

et al. 2020

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“…While HCMV host entry is hard to track, the ubiquity of mammalian CMV implies that their parasitism long preceded human emergence and that animal and human CMVs should behave similarly. Orally inoculated rhesus CMV can infect macaques ( 6 ). However, experimental inoculation involves giving high virus doses to sedated animals, making respiratory contamination hard to exclude, and again, no oral infection site has been identified.…”

Section: Introductionmentioning

confidence: 99%

Murine Cytomegalovirus Exploits Olfaction To Enter New Hosts

Farrell

Lawler

Tan

et al. 2016

mBio

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Viruses transmit via the environmental and social interactions of their hosts. Herpesviruses have colonized mammals since their earliest origins, suggesting that they exploit ancient, common pathways. Cytomegaloviruses (CMVs) are assumed to enter new hosts orally, but no site has been identified. We show by live imaging that murine CMV (MCMV) infects nasally rather than orally, both after experimental virus uptake and during natural transmission. Replication-deficient virions revealed the primary target as olfactory neurons. Local, nasal replication by wild-type MCMV was not extensive, but there was rapid systemic spread, associated with macrophage infection. A long-term, transmissible infection was then maintained in the salivary glands. The viral m131/m129 chemokine homolog, which influences tropism, promoted salivary gland colonization after nasal entry but was not required for entry per se. The capacity of MCMV to transmit via olfaction, together with previous demonstrations of experimental olfactory infection by murid herpesvirus 4 (MuHV-4) and herpes simplex virus 1 (HSV-1), suggest that this is a common, conserved route of mammalian herpesvirus entry.

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“…Thus, direct inoculation of RhCMV in naïve rhesus monkeys via subcutaneous or IV routes causes quantifiable, persistent infection, which allows assessment of the efficacy of prophylactic strategies. Oral RhCMV challenge and natural vertical transmission models via co-housing with RhCMV-seronegative monkeys are also being trialed as more physiologically-relevant challenge models that can better recapitulate human CMV transmission [39]. …”

Section: Rhcmv Acquisition and Persistencementioning

confidence: 99%

Rhesus monkeys for a nonhuman primate model of cytomegalovirus infections

Itell

Kaur

Deere

et al. 2017

Current Opinion in Virology

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Human cytomegalovirus (HCMV) is the leading opportunistic viral infection in solid organ transplant patients and is the most common congenitally transmitted pathogen worldwide. Despite the significant burden of disease HCMV causes in immunosuppressed patients and infected newborns, there are no licensed preventative vaccines or effective immunotherapeutic treatments for HCMV, largely due to our incomplete understanding of the immune correlates of protection against HCMV infection and disease. Though CMV species-specificity imposes an additional challenge in defining a suitable animal model for HCMV, nonhuman primate (NHP) CMVs are the most genetically related to HCMV. In this review, we discuss the advantages and applicability of rhesus monkey models for studying HCMV infections and pathogenesis and ultimately informing vaccine development.

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Use of specific‐pathogen‐free (SPF) rhesus macaques to better model oral pediatric cytomegalovirus infection

Cited by 13 publications

References 22 publications

Intrahost cytomegalovirus population genetics following antibody pretreatment in a monkey model of congenital transmission

Intrahost cytomegalovirus population genetics following antibody pretreatment in a monkey model of congenital transmission

Murine Cytomegalovirus Exploits Olfaction To Enter New Hosts

Rhesus monkeys for a nonhuman primate model of cytomegalovirus infections

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