Immune Responses to the Major Capsid Protein during Parvovirus Infection of Rats

Abstract

Rat virus (RV) is a common parvovirus of laboratory rodents which can disrupt rat-based research. Prenatal or perinatal infection can be pathogenic or lead to persistent infection, whereas infection of adult rats is typically self-limiting. Effects on the host immune system have been documented during RV infection, but little is known about immune responses necessary for viral clearance. Our studies were conducted to identify humoral and cellular responses to the predominant capsid protein, VP2, during experimental infection of adult rats. We observed VP2-specific proliferation, gamma interferon production, and an immunoglobulin G2a humoral response that is maintained for at least 35 days following RV infection. These results strongly suggest the induction of virus-specific Th1-mediated immunity.Parvoviruses are nonenveloped viruses with a singlestranded genome of approximately 5 kb. Viral replication is dependent on many cellular functions, particularly those expressed during S phase of the cell cycle (7). Rodent parvoviruses encode two classes of proteins: nonstructural (NS) proteins and structural or capsid proteins (VP). NS proteins are involved in viral replication, transcription, and cytotoxicity. VP1 comprises 15% of the icosahedral virion, and its coding sequence contains all of VP2 plus 140 additional N-terminal amino acids. VP2 is the predominant capsid protein, accounting for approximately 85% of the virion. VP3, a cleavage product of VP2, is present in small, varying amounts in DNAcontaining virions.A recent national survey found that parvovirus infections are highly prevalent among laboratory rats and mice (17). Infection with some of these agents can be lethal in fetal or perinatal animals, probably due to high numbers of mitotically active cells that serve as targets for cytolytic viral replication. Larger impacts on biomedical research result from clinically silent infections in infant or adult rodents in which biological processes and immune responses are altered. Specifically, infections with murine parvoviruses such as mouse minute virus and mouse parvovirus are known to inhibit several T-cell effector functions in vitro (2, 8); suppress antigen-induced proliferation of specific cloned T cells (18); augment the rate of tumor, allogeneic, and syngeneic graft rejection; and modulate other T-cell effector functions (19,21). In addition, infection with rat virus (RV), the prototypic parvovirus of rats, can decrease lymphocyte viability and suppress proliferative responses to alloantigens (4), diminish responses of mixed lymphocyte culture and cytolytic T cells from peripheral and mesenteric lymph nodes (20), alter humoral responses to ovalbumin (5), and provoke autoimmune diabetes in the diabetes-resistant strain of Biobreeding/Worcester (BB/WOR) rats (3,5,13).Despite the impact of these agents on host immunity, little is known about immune responses to rodent parvoviruses. It is known that rats develop antiviral antibodies and perivascular mononuclear cell infiltrates in infected tissues (10,14)....

Prevention of Virus-Induced Type 1 Diabetes with Antibiotic Therapy

“…Levels of transcripts for KRV capsid viral protein 2 (VP2) were also assessed on day 5 postinfection. The presence of KRV VP2 mRNA is indicative of viral replication (48,49). The data presented in Fig.…”

Humoral immune responses against minute virus of mice vectors

“…Already 4 days after virus inoculation, an anti‐viral IgM response could be observed which was replaced by an IgG response a few days later. In two recent studies immune responses in rats against rat virus polypeptides were reported 22, 41. An early anti‐VP2 capsid protein IgM response was found 7 days after virus inoculation and anti‐VP2 antibodies of the IgG2a isotype were more prominent than those belonging to the IgG1 subclass at all time points up to 35 days following infection.…”

“…The virus spreads in many organs (brain, lung, heart, liver, spleen) in which progeny infectious particles can be detected from 3 to at least 9 days post‐infection 21. The experimental infection of juvenile and adult rodents with parvoviruses elicits the production of anti‐viral humoral responses within 5–14 days after administration of the virus which control the viremia 22–25. On the other hand, virtually nothing is known about cellular immunity induced by autonomous parvovirus infections.…”

Medical Management and Diagnostic Approaches

“…Experimentally, it has been shown that sensitive antibody determination tests can identify seroconversion in a period as short as 1 week postexposure for rats infected with agents such as the rat coronavirus/sialodacryoadenitis virus (RCV/SDAV) (Smith, 1983) and the rat virus (RV) parvovirus (Ball-Goodrich et al, 2002). The time it takes a sentinel to be exposed to endemic infection would be expected to vary depending on specifics such as (1) the relative density of sentinels, (2) the frequency of cage changing and soiled bedding transfer, (3) the percentage of principal cages that have bedding sampled at each change, (4) the caging system in place, (5) the prevalence and transmissibility of the infectious agent present, and (6) possibly the macroenvironmental characteristics of the room, such as relative humidity and ventilation.…”