Vascular changes represent a characteristic feature of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection leading to a breakdown of the vascular barrier and subsequent edema formation. The aim of this study was to provide a detailed characterization of the vascular alterations during SARS-CoV-2 infection and to evaluate the impaired vascular integrity. Groups of ten golden Syrian hamsters were infected intranasally with SARS-CoV-2 or phosphate-buffered saline (mock infection). Necropsies were performed at 1, 3, 6, and 14 days post-infection (dpi). Lung samples were investigated using hematoxylin and eosin, alcian blue, immunohistochemistry targeting aquaporin 1, CD3, CD204, CD31, laminin, myeloperoxidase, SARS-CoV-2 nucleoprotein, and transmission electron microscopy. SARS-CoV-2 infected animals showed endothelial hypertrophy, endothelialitis, and vasculitis. Inflammation mainly consisted of macrophages and lower numbers of T-lymphocytes and neutrophils/heterophils infiltrating the vascular walls as well as the perivascular region at 3 and 6 dpi. Affected vessels showed edema formation in association with loss of aquaporin 1 on endothelial cells. In addition, an ultrastructural investigation revealed disruption of the endothelium. Summarized, the presented findings indicate that loss of aquaporin 1 entails the loss of intercellular junctions resulting in paracellular leakage of edema as a key pathogenic mechanism in SARS-CoV-2 triggered pulmonary lesions.

A retrospective study was performed to characterize malignant lymphomas of 16 Simian immunodeficiency virus (SIV)-infected rhesus monkeys ( Macaca mulatta), 2–9 years of age, on the basis of clinical data, histologic and immunophenotypic results, and cell death indices compiled with the TdT-mediated X-duTP nick end labeling method. We particularly focused on providing immunohistochemical evidence of expression products of EBNA2, Bcl2, c-Myc, P21, P53, and Bc16. Results were compared with data from the literature on human HIV-associated lymphomas. According to the updated Kiel classification, the lymphomas were classified as 11 centroblastic lymphomas, three immunoblastic lymphomas, one Burkitt-like lymphoma, and one immunocytoma. Using antibodies to CD20, the B-cell origin of tumor cells was demonstrated. SIV antigen was not demonstrated in the tumor cells. Infection with rhesus lymphocryptovirus was present in 94% of the monkeys. Lymphomas revealed expression of Bc12 in 15/16 (94%), c-Myc in 14/16 (88%), P21 in 10/16 (63%), P53 in 12/16 (75%), and Bc16 in 1/16 (6%) monkeys. This study provided evidence that the expression of these gene products, which are thought to play an important role in cell proliferation and apoptosis in HIV- and non-HIV-associated lymphomas, are also involved in the pathogenesis of lymphomas in SIVinfected rhesus monkeys. A tentative relationship between the described gene products and the cell death indices was established for the expression of Bc12. The present primate model represents a suitable animal model for studying the pathogenesis of AIDS-associated lymphomas.

Smallpox, one of the most destructive diseases, has been successfully eradicated through a worldwide vaccination campaign. Since immunization programs have been stopped, the number of people with vaccinia virus induced immunity is declining. This leads to an increase in orthopoxvirus (OPXV) infections in humans, as well as in animals. Additionally, potential abuse of Variola virus (VARV), the causative agent of smallpox, or monkeypox virus, as agents of bioterrorism, has renewed interest in development of antiviral therapeutics and of safer vaccines. Due to its high risk potential, research with VARV is restricted to two laboratories worldwide. Therefore, numerous animal models of other OPXV infections have been developed in the last decades. Non-human primates are especially suitable due to their close relationship to humans. This article provides a review about on non-human primate models of orthopoxvirus infections.

Although the risk of a herpes B virus (Cercopithecine herpes virus 1) infection is low, the clinical course of the infectious disease is generally unfavourable. A high safety standard can be achieved if people with professional contact to primates apply proper organisational, technical and personal safety precautions. The risk can be considerably reduced if animal keepers, laboratory assistants and scientists receive adequate information about the pathology of herpes B virus and are well trained in the necessary procedures and the precautions. For this reason, comprehensive and regular training, information and instruction must be provided to all primate workers and to laboratory workers who come into contact with potentially infectious material. After potential contamination, the risk for the affected worker must be assessed immediately and post-exposure chemoprophylaxis performed if necessary. This necessitates internal risk assessment. An interdisciplinary group of experts has developed an action plan for Germany.

Common marmosets (Callithrix jacchus) are small non-human primates (NHPs) that are often used for respiratory research. Translational animal models of various pulmonary diseases in marmosets have been developed in favor of models in old world monkeys (OWM, e.g., rhesus or cynomolgus monkeys). The marmoset has the size of a rat (350–450 g), is easier to handle, and the husbandry, care, and management of colonies is much easier compared to OWMs. In contrast to rodents, marmosets provide a high homology to humans, which become especially visible in lung architecture and branching pattern. Features of inflammatory (e.g., COPD) pulmonary diseases can be modeled in marmosets as well the species is used to study bacterial and viral infection. Models for human melioidosis, tuberculosis, anthrax, as well as infections with SARS-associated coronavirus (SARS-CoV), influenza A virus and adenovirus are already established. Toxicological studies often use marmoset monkeys for the advantage of immunological identical twins that are produced by a Callitrichinae-specific placentation type, which ultimately causes blood chimerism. Relatively new approaches in gene therapy use marmosets for respiratory disease research. In this review we will give an overview of existing respiratory marmoset models and their impact on biomedical research.

Tubuloreticular structures (TRS) are considered to be a specific ultrastructural marker for AIDS in various organs. Experimental SIV infection in rhesus macaques is the most appropriate animal model of HIV infection. In 8 rhesus monkeys, experimentally infected with SIVmac251/MPBC, rectum biopsies were taken prior to and post infection (day 3; 1, 2, 4, 12 weeks p.i.) and were investigated by transmissionelectron microscopy to determine incidence and extent of tubuloreticular structures as well as affected cells. From the first week p.i. on TRS were found in all experimental animals as tubuli with a diameter of 20–30 nm. The tubuli were arranged in regular paracristalline formations and formed intracytoplasmatic heterogenous, polymorph accumulations, which were localized close to the endoplasmatic reticulum. In the rectal lamina propria macrophages, endothelial cells, plasma cells, lymphocytes, fibroblasts, and neutrophilic granulocytes were the affected cell types. In 5 control biopsies TRS were detected, too, but, in contrast to SIV-infected animals, they appeared only singular and very small. The results indicate that TRS are a characteristic morphologic criteria of intestinal SIV infection. They appear in very early stages of the infection. In the rectum, they can be detected as bigger, conspicuous, and abundant formations in several cells and have a restricted diagnostic and prognostic validity.