Experimental infection of cynomolgus monkeys with simian parvovirus

Abstract

Simian parvovirus is a recently discovered parvovirus that was first isolated from cynomolgus monkeys. It is similar to human B19 parvovirus in terms of virus genome, tropism for erythroid cells, and characteristic pathology in natural infections. Cynomolgus monkeys were infected with simian parvovirus to investigate their potential usefulness as an animal model of human B19 parvovirus. Six adult female cynomolgus monkeys were inoculated with purified simian parvovirus by the intravenous or intranasal route and monitored for evidence of clinical abnormalities; this included the preparation of complete hematological profiles. Viremia and simian parvovirus-specific antibody were determined in infected monkeys by dot blot and Western blot assays, respectively. Bone marrow was examined at necropsy 6, 10, or 15 days postinfection. All of the monkeys developed a smoldering, low-grade viremia that peaked approximately 10 to 12 days after inoculation. Peak viremia coincided with the appearance of specific antibody and was followed by sudden clearance of the virus and complete, but transient, absence of reticulocytes from the peripheral blood. Clinical signs were mild and involved mainly anorexia and slight weight loss. Infection was associated with a mild decrease in hemoglobin, hematocrit, and erythrocyte numbers. Bone marrow showed marked destruction of erythroid cells coincident with peak viremia. Our findings indicate that infection of healthy monkeys by simian parvovirus is self-limited and mild, with transient cessation of erythropoiesis. Our study has reproduced Koch's postulates and further shown that simian parvovirus infection of monkeys is almost identical to human B19 parvovirus infection of humans. Accordingly, this animal model may prove valuable in the study of the pathogenesis of B19 virus infection.

The Simian Parvoviruses

“…Cynomolgus monkeys were experimentally inoculated with SPV to investigate their potential usefulness as an animal model of human B19 parvovirus. 18 Six adult female cynomolgus monkeys received purified SPV by intravenous or intranasal routes. Infected monkeys were monitored for evidence of clinical abnormalities, including complete haematological profiles.…”

Comprehensive identification of high-frequency and co-occurring Mafa-B, Mafa-DQB1, and Mafa-DRB alleles in cynomolgus macaques of Vietnamese origin

“…With the 1978 ban on exportation of rhesus macaques (Macaca mulatta) from India, the cynomolgus macaque (Macaca fascicularis) became an increasingly useful animal model for various diseases, including diabetes, severe acute respiratory syndrome (SARS), tuberculosis, simian immunodeficiency virus (SIV), renal transplantation, and pharmacodynamic evaluation [1][2][3][4]. Major histocompatibility complex (MHC) class I and class II molecules play key roles in immune regulatory processes by presenting peptides of intracellular or extracellular origin to CD8 ϩ or CD4 ϩ T cells, respectively.…”

Characterization of the major histocompatibility complex class II DOB, DPB1, and DQB1 alleles in cynomolgus macaques of Vietnamese origin

“…With the 1978 ban on exportation of Rhesus macaques from India, researchers have become increasingly interested in an alternative macaque, the cynomolgus macaque, which has a shorter breeding cycle, a docile personality, and requires lower dosages of drugs. The cynomolgus macaque (Macaca fascicularis), also known as the crab-eating monkey or long-tailed macaque, is used mainly in animal models of diabetes, renal transplantation, virological research, SARS, tuberculosis, studies of the pathogenesis of simian immunodeficiency virus (SIV), and pharmacodynamic evaluation (O'Sullivan et al 1997;Menninger et al 2002;McAuliffe et al 2004;Reed et al 2009). Owing to the need for reliable data on experimental drug reactions provided by animal models, researchers have focused on genes of the immune system of cynomolgus monkeys, in particular, the genes of the major histocompatibility complex (MHC).…”

“…DO is a nonclassical class II heterodimer that consists of α and β chains, which are encoded by the DOA and DOB genes located in the MHC class II region. The function of MHC-DO is poorly understood; it may act as a negative regulator by binding to HLA-DM and inhibiting the exchange reaction of class IIassociated invariant chain peptides for antigenic peptides (Fernandez-Donoso et al 1970;O'Sullivan et al 1997). HLA-DPB1 alleles have been demonstrated to be involved in corneal and renal transplantation, myasthenia gravis, multiple sclerosis, Hodgkin's disease, Beryllium disease, and sarcoidosis.…”