Replication of Clinical Measles Virus Strains in Hispid Cotton Rats

Abstract

An alternative model to nonhuman primates to study measles virus (MV) pathogenesis, to evaluate potential MV vaccines, or to screen for potential antivirals effective against this virus is highly desirable. The laboratory-adapted Edmonston strain of MV has been reported to replicate in the lungs of hispid cotton rats following intranasal inoculation, immunosuppress infected animals, and disseminate widely from the lungs, making these animals a candidate model. However, clinical MV strains have generally not been found to grow in these animals, limiting the utility and acceptance of this model. In the present studies we demonstrate reproducible replication of several clinical MV strains in hispid cotton rats. As with the Edmonston strain, leukocytes appear to be the primary target cells of these viruses following intranasal inoculation, and extrapulmonary dissemination is common. It is also demonstrated that prior MV infection or immunization of test animals with MV vaccine prevents pulmonary tract infection. These findings should make the MV-cotton rat model more acceptable.

Extent of Measles Virus Spread and Immune Suppression Differentiates between Wild-Type and Vaccine Strains in the Cotton Rat Model ( Sigmodon hispidus )

“…However, the ability of vaccine versus wild-type virus to inhibit the proliferation of spleen cells ex vivo was not investigated. Using the lymphoid B95-8 cell line as indicator cells (12), Wyde et al were able to recover clinical isolates of MV efficiently from a lung tissue homogenate of infected cotton rats (33). One clinical isolate (MO2) was tested for viral spread and was found (apart from the lungs) sometimes in mediastinal lymph node cells (9 of 16 animals) and spleen (2 of 16 animals) but not in other organs.…”

The Quest for a Small Animal Model for HIV Infection and Disease

“…For over a decade, S. hispidus remained the prime animal model for polio until supplanted by monkeys and mice, with mice requiring extensive adaptation of virus. Since then, the cotton rat has been extensively used as a model to study different aspects of infection by respiratory syncytial virus (Li et al, 2000;Malley et al, 1998;Prince et al, 2001;Prince et al, 1978;Prince et al, 1999;Rodriguez et al, 1997;Tang et al, 2001), influenza A and B (Sadowski et al, 1987), parainfluenza viruses types 1, 2, and 3 (Ottolini et al, 2000;Porter et al, 1991;Prince et al, 2001;Sadowski et al, 1987), herpes simplex virus type 1 (HSV-1) (Lewandowski et al, 2002), HSV-2 (Yim et al, 2005), measles virus (Niewiesk, 2001;Niewiesk et al, 1997;Wyde et al, 1999), as well as several serotypes of adenovirus (Brunori et al, 2001;Ginsberg et al, 1989;Ginsberg, Moldawer, and Prince, 1999;Rojas-Martinez et al, 1998;Tsubota et al, 1998;Wildner and Morris, 2002). Finally, cotton rats are also natural reservoirs of several viruses of importance as emerging human pathogens.…”

AttenuatedSalmonella entericaSerovar Typhi andShigella flexneri2a Strains Mucosally Deliver DNA Vaccines Encoding Measles Virus Hemagglutinin, Inducing Specific Immune Responses and Protection in Cotton Rats

“…After i.n. inoculation of cotton rats with wild-type MV, virus replication ensues, allowing recovery of virus from lung tissue, bronchial cells, and draining lymph nodes, as well as from the spleen (31,51,52). Vaccine candidates that elicit sufficiently high titers of neutralizing antibodies and MV-specific T-cell responses can confer protection against subsequent challenge with wild-type virus (41,42,50,53).…”

“…challenge, thereby allowing studies of pathogenesis, infection, and immunity elicited by vaccines (31,33,(51)(52)(53). After i.n.…”