Eliminating Potential Effects of Other Infections During Selection of Nonhuman Primates for COVID-19 Research.

The study of nonhuman primates (NHP) can provide significant insights into our understanding numerous infectious agents. The etiological agent of COVID-19, SARS-CoV-2 virus, first emerged in 2019 and has so far been responsible for the deaths of over 4 million people globally. In the frenzied search to understand its pathogenesis and immunology and to find measures for prevention and control of this pandemic disease, NHP, particularly macaques, are the preferred model because they manifest similar clinical signs and immunologic features as humans. However, possible latent, subclinical, and opportunistic infections not previously detected in animals participating in a study may obscure experimental results and confound data interpretations in testing treatments and vaccine studies for COVID-19. Certain pathophysiologic changes that occur with SARS-CoV-2 virus infection are similar to those of simian pathogens. The current review discusses numerous coinfections of COVID-19 with other diseases and describes possible outcomes and mechanisms in COVID-19 studies of NHP that have coinfections. Due to the urgency triggered by the pandemic, screening that is more rigorous than usual is necessary to limit background noise and maximize the reliability of data from NHP COVID-19 studies. Screening for influenza virus, selected respiratory bacteria, and regional endemic pathogens such as vector-borne agents, together with the animal's individual exposure history, should be the main considerations in selecting a NHP for a COVID-19 study. In addition, because NHP are susceptible to the SARS-CoV-2 virus, management and surveillance measures should be established to prevent transmission to healthy animals from infected colony animals and husbandry staff. This review presents compiled data on the use of NHP in COVID-19 studies, emphasizing the need to create the most reliable NHP model for those studies by extensive screening for other pathogens.

Cellular Immune Responses against Simian T-Lymphotropic Virus Type 1 Target Tax in Infected Baboons.

UNLABELLED: There are currently 5 million to 10 million human T-lymphotropic virus type 1 (HTLV-1)-infected people, and many of them will develop severe complications resulting from this infection. A vaccine is urgently needed in areas where HTLV-1 is endemic. Many vaccines are best tested in nonhuman primate animal models. As a first step in designing an effective HTLV-1 vaccine, we defined the CD8(+) and CD4(+) T cell response against simian T-lymphotropic virus type 1 (STLV-1), a virus closely related to HTLV-1, in olive baboons (Papio anubis). Consistent with persistent antigenic exposure, we observed that STLV-1-specific CD8(+) T cells displayed an effector memory phenotype and usually expressed CD107a, gamma interferon (IFN-γ), and tumor necrosis factor alpha (TNF-α). To assess the viral targets of the cellular immune response in STLV-1-infected animals, we used intracellular cytokine staining to detect responses against overlapping peptides covering the entire STLV-1 proteome. Our results show that, similarly to humans, the baboon CD8(+) T cell response narrowly targeted the Tax protein. Our findings suggest that the STLV-1-infected baboon model may recapitulate some of the important aspects of the human response against HTLV-1 and could be an important tool for the development of immune-based therapy and prophylaxis. IMPORTANCE: HTLV-1 infection can lead to many different and often fatal conditions. A vaccine deployed in areas of high prevalence might reduce the incidence of HTLV-1-induced disease. Unfortunately, there are very few animal models of HTLV-1 infection useful for testing vaccine approaches. Here we describe cellular immune responses in baboons against a closely related virus, STLV-1. We show for the first time that the immune response against STLV-1 in naturally infected baboons is largely directed against the Tax protein. Similar findings in humans and the sequence similarity between the human and baboon viruses suggest that the STLV-1-infected baboon model might be useful for developing a vaccine against HTLV-1.

A simian hemorrhagic fever virus isolate from persistently infected baboons efficiently induces hemorrhagic fever disease in Japanese macaques.

Simian hemorrhagic fever virus is an arterivirus that naturally infects species of African nonhuman primates causing acute or persistent asymptomatic infections. Although it was previously estimated that 1% of baboons are SHFV-positive, more than 10% of wild-caught and captive-bred baboons tested were SHFV positive and the infections persisted for more than 10 years with detectable virus in the blood (100-1000 genomes/ml). The sequences of two baboon SHFV isolates that were amplified by a single passage in primary macaque macrophages had a high degree of identity to each other as well as to the genome of SHFV-LVR, a laboratory strain isolated in the 1960s. Infection of Japanese macaques with 100PFU of a baboon isolate consistently produced high level viremia, pro-inflammatory cytokines, elevated tissue factor levels and clinical signs indicating coagulation defects. The baboon virus isolate provides a reliable BSL2 model of viral hemorrhagic fever disease in macaques.