A model of lymphocryptovirus-associated post-transplant lymphoproliferative disorder in immunosuppressed Mauritian cynomolgus macaques.

Immunocompromised individuals are at risk for developing lymphocryptovirus-associated lymphoproliferative diseases, such as Epstein Barr virus (EBV)-associated B cell lymphomas and post-transplant lymphoproliferative disorder (PTLD). We previously reported development of cynomolgus lymphocryptovirus (CyLCV)-associated PTLD in Mauritian cynomolgus macaques (MCMs) undergoing hematopoietic stem cell transplantation (HSCT), which mirrored EBV-PTLD in transplant patients. Here, we sought to develop a MCM model of lymphocryptovirus-associated lymphoproliferative disease in immunosuppressed MCMs without HSCT.

Aerosol delivery of SARS-CoV-2 human monoclonal antibodies in macaques limits viral replication and lung pathology.

Passively administered monoclonal antibodies (mAbs) given before or after viral infection can prevent or blunt disease. Here, we examine the efficacy of aerosol mAb delivery to prevent infection and disease in rhesus macaques inoculated with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Delta variant via intranasal and intratracheal routes. SARS-CoV-2 human mAbs or a human mAb directed to respiratory syncytial virus (RSV) are nebulized and delivered using positive airflow via facemask to sedated macaques pre- and post-infection.

Allogeneic immunity clears latent virus following allogeneic stem cell transplantation in SIV-infected ART-suppressed macaques.

Allogeneic hematopoietic stem cell transplantation (alloHSCT) from donors lacking C-C chemokine receptor 5 (CCR5) can cure HIV, yet mechanisms remain speculative. To define how alloHSCT mediates HIV cure, we performed MHC-matched alloHSCT in SIV, anti-retroviral therapy (ART)-suppressed Mauritian cynomolgus macaques (MCMs) and demonstrated that allogeneic immunity was the major driver of reservoir clearance, occurring first in peripheral blood, then peripheral lymph nodes, and finally in mesenteric lymph nodes draining the gastrointestinal tract. While allogeneic immunity could extirpate the latent viral reservoir and did so in two alloHSCT-recipient MCMs that remained aviremic >2.

Viral opportunistic infections in Mauritian cynomolgus macaques undergoing allogeneic stem cell transplantation mirror human transplant infectious disease complications.

Allogeneic hematopoietic stem cell transplantation (HSCT) and xenotransplantation are accompanied by viral reactivations and virus-associated complications resulting from immune deficiency. Here, in a Mauritian cynomolgus macaque model of fully MHC-matched allogeneic HSCT, we report reactivations of cynomolgus polyomavirus, lymphocryptovirus, and cytomegalovirus, macaque viruses analogous to HSCT-associated human counterparts BK virus, Epstein-Barr virus, and human cytomegalovirus. Viral replication in recipient macaques resulted in characteristic disease manifestations observed in HSCT patients, such as polyomavirus-associated hemorrhagic cystitis and tubulointerstitial nephritis or lymphocryptovirus-associated post-transplant lymphoproliferative disorder.

Single-dose bNAb cocktail or abbreviated ART post-exposure regimens achieve tight SHIV control without adaptive immunity.

Vertical transmission accounts for most human immunodeficiency virus (HIV) infection in children, and treatments for newborns are needed to abrogate infection or limit disease progression. We showed previously that short-term broadly neutralizing antibody (bNAb) therapy given 24 h after oral exposure cleared simian-human immunodeficiency virus (SHIV) in a macaque model of perinatal infection. Here, we report that all infants given either a single dose of bNAbs at 30 h, or a 21-day triple-drug ART regimen at 48 h, are aviremic with almost no virus in tissues.

Allogeneic stem cell transplantation in fully MHC-matched Mauritian cynomolgus macaques recapitulates diverse human clinical outcomes.

Allogeneic hematopoietic stem cell transplantation (HSCT) is a critically important therapy for hematological malignancies, inborn errors of metabolism, and immunodeficiency disorders, yet complications such as graft-vs.-host disease (GvHD) limit survival. Development of anti-GvHD therapies that do not adversely affect susceptibility to infection or graft-vs.

Ventricular Parasystole in a Neonatal Rhesus Macaque ().

A 6-d-old Indian-origin female rhesus macaque (Macaca mulatta) presented with bradycardia shortly after sedation with ketamine. No other cardiac abnormalities were apparent. Approximately 2 wk after the initial presentation, the macaque was again bradycardic and exhibited a regularly irregular arrhythmia on a prestudy examination.

Early short-term treatment with neutralizing human monoclonal antibodies halts SHIV infection in infant macaques.

Prevention of mother-to-child transmission (MTCT) of HIV remains a major objective where antenatal care is not readily accessible. We tested HIV-1-specific human neutralizing monoclonal antibodies (NmAbs) as a post-exposure therapy in an infant macaque model for intrapartum MTCT. One-month-old rhesus macaques were inoculated orally with the simian-human immunodeficiency virus SHIVSF162P3.

Detection of elephant endotheliotropic herpesvirus infection among healthy Asian elephants (Elephas maximus) in South India.

Elephant endotheliotropic herpesviruses (EEHVs) can cause fatal hemorrhagic disease in Asian (Elephas maximus) and African (Loxodonta africana) elephants. Of the seven known EEHV species, EEHV1 is recognized as the most common cause of hemorrhagic disease among Asian elephants in human care worldwide. Recent data collected from ex situ Asian elephants located in multiple North American and European institutions suggest that subclinical EEHV1 infection is common in this population of elephants.

Acute phase protein expression during elephant endotheliotropic herpesvirus-1 viremia in Asian elephants (Elephas maximus).

Infection of Asian elephants (Elephas maximus) with elephant endotheliotropic herpesvirus (EEHV) can be associated with rapid, lethal hemorrhagic disease and has been documented in elephant herds in human care and in the wild. Recent reports describe real-time quantitative polymerase chain reaction (qPCR) assays used to monitor clinically ill elephants and also to detect subclinical EEHV1 infection in apparently healthy Asian elephants. Acute phase proteins have been demonstrated to increase with a variety of infectious etiologies in domesticated mammals but have not yet been described in elephants.

Prenatal passive transfer of maternal immunity in Asian elephants (Elephas maximus).

Asian (Elephas maximus) and African (Loxodonta africana) elephants exhibit characteristics of endotheliochorial placentation, which is common in carnivore species and is associated with modest maternal to fetal transplacental antibody transfer. However, it remains unknown whether the bulk of passive immune transfer in elephants is achieved prenatally or postnatally through ingestion of colostrum, as has been documented for horses, a species whose medical knowledgebase is often extrapolated for elephants. To address this issue, we took advantage of the fact that many zoo elephants are immunized with tetanus toxoid and/or rabies vaccines as part of their routine health care, allowing a comparison of serum antibody levels against these antigens between dams and neonates.

Elephant endotheliotropic herpesvirus 5, a newly recognized elephant herpesvirus associated with clinical and subclinical infections in captive Asian elephants (Elephas maximus).

Elephant endotheliotropic herpesviruses (EEHVs) can cause acute hemorrhagic disease with high mortality rates in Asian elephants (Elephas maximus). Recently, a new EEHV type known as EEHV5 has been described, but its prevalence and clinical significance remain unknown. In this report, an outbreak of EEHV5 infection in a herd of captive Asian elephants in a zoo was characterized.

Kinetics of viral loads and genotypic analysis of elephant endotheliotropic herpesvirus-1 infection in captive Asian elephants (Elephas maximus).

Elephant endotheliotropic herpesviruses (EEHVs) can cause fatal hemorrhagic disease in juvenile Asian elephants (Elphas maximus); however, sporadic shedding of virus in trunk washes collected from healthy elephants also has been detected. Data regarding the relationship of viral loads in blood compared with trunk washes are lacking, and questions about whether elephants can undergo multiple infections with EEHVs have not been addressed previously. Real-time quantitative polymerase chain reaction was used to determine the kinetics of EEHV1 loads, and genotypic analysis was performed on EEHV1 DNA detected in various fluid samples obtained from five Asian elephants that survived detectable EEHV1 DNAemia on at least two separate occasions.

Development and validation of quantitative real-time polymerase chain reaction assays to detect elephant endotheliotropic herpesviruses-2, 3, 4, 5, and 6.

Elephant endotheliotropic herpesviruses (EEHVs) can cause lethal hemorrhagic disease in both African and Asian elephants. At least seven EEHV types have been described, and sensitive real-time PCR tests have been developed for EEHV1A and 1B, which are associated with the majority of characterized Asian elephant deaths. Despite growing knowledge of the different EEHV types, the prevalence of each type within African and Asian elephants remains to be determined and there is considerable need for diagnostic tests to detect and discriminate between each EEHV species for clinical management of African and Asian elephants that develop illness from one or more of these viruses.

Detection of pathogenic elephant endotheliotropic herpesvirus in routine trunk washes from healthy adult Asian elephants (Elephas maximus) by use of a real-time quantitative polymerase chain reaction assay.

Objective: To investigate the pathogenesis and transmission of elephant endotheliotropic herpesvirus (EEHV1) by analyzing various elephant fluid samples with a novel EEHV1-specific real-time PCR assay.

Animals: 5 apparently healthy captive Asian elephants (Elephas maximus) from the same herd.

Procedures: A real-time PCR assay was developed that specifically detects EEHV1.