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Structural determinants of tissue tropism and in vivo pathogenicity for the parvovirus minute virus of mice.

Two strains of the parvovirus minute virus of mice (MVM), the immunosuppressive (MVMi) and the prototype (MVMp) strains, display disparate in vitro tropism and in vivo pathogenicity. We report the crystal structures of MVMp virus-like particles (MVMp(b)) and native wild-type (wt) empty capsids (MVMp(e)), determined and refined to 3.25 and 3.75 A resolution, respectively, and their comparison to the structure of MVMi, also refined to 3.5 A resolution in this study. A comparison of the MVMp(b) and MVMp(e) capsids showed their structures to be the same, providing structural verification that some heterologously expressed parvovirus capsids are indistinguishable from wt capsids produced in host cells. The structures of MVMi and MVMp capsids were almost identical, but local surface conformational differences clustered from symmetry-related capsid proteins at three specific domains: (i) the icosahedral fivefold axis, (ii) the "shoulder" of the protrusion at the icosahedral threefold axis, and (iii) the area surrounding the depression at the icosahedral twofold axis. The latter two domains contain important determinants of MVM in vitro tropism (residues 317 and 321) and forward mutation residues (residues 399, 460, 553, and 558) conferring fibrotropism on MVMi. Furthermore, these structural differences between the MVM strains colocalize with tropism and pathogenicity determinants mapped for other autonomous parvovirus capsids, highlighting the importance of common parvovirus capsid regions in the control of virus-host interactions.

Capsid↗

Parvovirus associated antigen in the synovial membrane of patients with rheumatoid arthritis.

Homogenates of synovium from patients with rheumatoid arthritis (RA) and osteoarthritis (OA) were centrifuged on caesium chloride density gradients to obtain isolates of a density similar to that of parvoviruses. Six of 11 RA isolates and none of six OA isolates reacted with an antiserum raised against a rheumatoid associated, parvovirus-like agent (RA-1 virus). An anti-B19 parvovirus antiserum did not react with any of the isolates tested. Electron microscopy of negatively stained preparations of the isolates showed that small particles of diameter 10 nm were abundant in most of the RA isolates (11/13) but absent from all OA isolates. Such particles, whose identification is unknown, were also present in RA-1 positive lysates prepared from cultured RA synovial cells. These results suggest that the RA-1 virus can be directly identified in RA synovial tissue and that the virus appears to be unrelated to the human B19 parvovirus.

Antigens, Viral↗

Canine parvovirus infection in Australia during 1980.

A questionnaire sent to all veterinary practitioners in Australia and many in New Zealand asking for details of their experience with canine parvovirus infections in 1980 elicited the following information. In 1980 explosive outbreaks of disease occurred in most parts of Australia. There was no obvious pattern of spread over the continent as a whole. In many cases outbreaks in country areas occurred after dog shows. Canine parvovirus enteritis affected all age groups with an overall mortality of 16 per cent. While the death rate in the young was high, most dogs responded well to fluid therapy. Canine parvovirus did not appear to be associated with clinical entities other than gastroenteritis and myocarditis. No connection with reproductive problems was established. Killed canine parvovirus vaccines were used extensively after the initial release for sale in July 1980. The vaccines appeared to be safe and effective at least in the short term. Problems arose only in vaccination of very young animals.

Animals↗

Canine parvovirus serology: a collaborative assay.

Fifteen laboratories were supplied with coded samples of canine sera for testing for the presence of antibodies against canine parvoviruses. One of these sera had been designated as a potential British standard canine parvovirus antiserum. Most of these laboratories were either providing a canine parvovirus serology service, or represented pharmaceutical companies which manufacture canine parvovirus vaccines for the United Kingdom market. No attempt was made to influence the test methods used. Thirteen of the laboratories used a haemagglutination inhibition test, three an enzyme-linked immunosorbent assay (ELISA), and two performed serum neutralisation tests. Three laboratories used two different techniques. Adequate analysis was possible only with the results of the haemagglutination inhibition tests. The variability of the results between laboratories could be partly controlled by the use of the standard serum. Much of the residual variability was associated with particular laboratories. The results from the vaccine manufacturers tended to be less variable than those from the diagnostic laboratories.

Animals↗

Canine coronavirus-associated puppy mortality without evidence of concurrent canine parvovirus infection.

This report presents 2 cases in which puppy fatalities were associated with canine coronavirus (CCV), but no evidence of concurrent canine parvovirus (CPV-2) disease was observed. Case 1 involved a 7-week-old, male short-haired Chihuahua, which had become lethargic 24 hours after purchase from a pet store. Within 72 hours, the puppy began to vomit, had diarrhea, and was admitted to the veterinary clinic, where it was placed on IV fluids. The parvovirus Cite test was negative. The puppy died within 12 hours of admission and was submitted for diagnostic workup. Gross pathology revealed an enteritis suggestive of CPV-2. Histopathology on intestines showed scattered dilated crypts with necrotic cellular debris and neutrophils. There was moderate depletion and necrosis of lymphoid follicles. Electron microscopy (EM) on intestinal contents was positive for coronavirus and negative for parvovirus. Immunohistochemistry (IHC) on gut sections was positive for CCV and negative for CPV-2. Case 2 was an 8-week-old, male Shih Tzu, which was admitted to the veterinary clinic exhibiting symptoms of severe gastroenteritis with abdominal pain. The referring veterinarian euthanized the puppy, and the entire body was submitted for diagnostic evaluation. Necropsy revealed a severe ileo-cecal intussusception and segmental necrotic enteritis of the small intestine. Electron microscopy of the intestinal contents was positive for coronavirus and negative for parvovirus. Immunohistochemistry on sections of affected gut were positive for CCV and negative for CPV-2. These cases emphasize the importance of pursuing a diagnosis of CCV in young puppies when CPV-2 disease has been ruled out by IHC.

Animals↗

Electron microscopic identification of parvovirus virions in erythroid-line cells in fatal hydrops fetalis.

Intrauterine infection with parvovirus B19 may lead to fatal hydrops fetalis. Intranuclear particles, consistent with parvovirus virions, within erythroid cells were readily identified on transmission electron microscopy of formalin-preserved material obtained at necropsy from a neonate and two fetuses in whom clinical and light microscopic criteria for parvovirus B19 infection were met. No such particles were seen in similar material from a neonate and two fetuses with erythroblastosis fetalis due to alpha-thalassemia, maternofetal Rh incompatibility, and an erythrocyte membrane protein defect. When other means of investigation are impracticable transmission electron microscopy is widely available and easily performed and may be of value in establishing a diagnosis of parvovirus B19 infection.

Adult↗

Systemic monocyte and T-cell activation in a patient with human parvovirus B19 infection.

Infection with human parvovirus B19 induces a biphasic disease. The initial phase has been associated with viremia. During the second phase of the disease, a spectrum of clinical syndromes can manifest, including erythema infectiosum, perinatal complications, and symmetric arthropathy that resembles rheumatoid arthritis. Although investigators have suspected that some of the second-phase symptoms are related to immune complex formation, the pathogenesis of parvovirus B19-induced clinical manifestations is not understood. Herein we describe a 63-year-old woman with malaise, fever, and symmetric polyarthritis who had IgM antibodies specific for parvovirus B19. Messenger RNA (mRNA) specific for interleukin (IL) 1 beta, IL 6, and interferon-gamma (IFN-gamma) was detected by polymerase chain reaction. Transcript concentrations were semiquantified by serial dilution of cells and determination of the minimal number of cells that provided a positive signal. Concentrations of IL 1 beta and IL 6 mRNA in peripheral blood mononuclear cells collected during acute disease were increased by the factor of 32 and 8, respectively. IFN-gamma was detected at a 16-fold increased concentration. Two months later, after the patient had experienced complete recovery, production of monokines and IFN-gamma was almost normalized. These data raise the possibility that acute parvovirus B19 infection is characterized by a widespread and systemic activation of monocytes, T cells, and natural killer cells. The correlation of increased cytokine mRNA levels and clinical symptoms suggests a potential role of proinflammatory monokines and lymphokines in disease manifestations.

Acute Disease↗

Histopathological changes of the brain in swine fetuses naturally infected with procine parvovirus.

During a period from 1971 to 1972, some cases of stillbirth and abortion associated with porcine parvovirus infection were recognized in swine herds in Japan. The brain was examined histopathologically in five stillborn piglets and four dead fetuses from which the parvoviruses had been isolated. Similar histological changes were observed in all the piglets and fetuses, except one piglet which was free from recognizable lesions. The brain lesions were considered to belong to the category of meningoencephalitis consisting of perivascular cuffing of proliferating adventitial cells and a few plasma cells. They were localized in the cerebral gray and white matter and leptomeninges, but not in the cerebellum. These histological lesions were thought to be pathognomonic to porcine parvovirus infection. The difference in brain lesions between porcine parvovirus infection and Japanese encephalitis virus infection was discussed.

Animals↗

Reproductive failure in swine associated with maternal seroconversion for porcine parvovirus.

Reproductive failure occurred in a swine herd in which the epizootiology of enteroviruses and the porcine parvovirus were being studied. Three virgin boars that were seropositive for the parvovirus were mated to seronegative, previously unmated gilts. The 11 gilts that farrowed had small litters, with high perinatal mortality. The remaining 12 gilts were marketed because of infertility, and the reproductive tracts were examined. Pathologic findings included early embryonal death attributed to viral infection. After the reproductive failure, all gifts and boars were seropositive for the parvovirus, suggesting that the reproductive failure was associated with a parvovirus infection.

Animals↗

[Diagnosis of parvovirus B19 infection in patients with secondary immunodeficiency diseases].

The method of immune-enzyme assay was used to examine 113 patients with secondary immunodeficiency, including 16 HIV-infected drug-addicts (group 1), 36 patients with cytomegalovirus infection (CMVI) and with immunoregating index CD4/CD8 below 1.0 (group 2), 30 patients with CMVI and with CD4/CD8 below 1.2 (group 3) and 31 patients with aplastic anemia and with anemia of unclear genesis (group 4), for parvovirus infection caused by parvovirus B19. As for groups 1 and 4, the antibodies were detected in 50 and 48.4% of cases; it is noteworthy that an active parvovirus infection was registered in the above groups more often than in groups 2 and 3. There were patients with the antibodies in group 2 by 1.8 times more than in group 3. It is suggested that the simultaneous impact of HIV, CMV and parvoviruses significantly aggravates the immunodeficiency and contributes to a more severe clinical course.

Antibodies, Viral↗

Morphological diagnosis of parvovirus B19 infection. A cytopathic effect easily recognized in air-dried, formalin-fixed bone marrow smears stained with hematoxylin-eosin or Wright-Giemsa.

Readily identifiable intranuclear inclusions characterize parvovirus B19 cytopathic effect in formalin-fixed, paraffin-embedded material. Such inclusions are not apparent in air-dried smears of bone marrow aspirates. Brief formalin fixation of bone marrow smears, followed by either hematoxylin-eosin or Wright-Giemsa staining, permitted easy detection of parvovirus B19 inclusions in material from a renal transplant recipient with parvovirus B19 infection documented serologically and by electron microscopy. Formalin fixation of bone marrow and peripheral blood smears before hematoxylin-eosin or Wright-Giemsa staining may simplify the morphological diagnosis of parvovirus B19 infection.

Bone Marrow Diseases↗

[Fluorescence serologic and histologic studies of antigen distribution in parvovirus infections in dogs and cats].

In organs known as replication sites of parvovirus and additionally in stratified squamous epithelia from different regions of 35 dogs with lethal parvovirus enteritis and 19 cats with lethal panleukopenia the distribution of antigen and the prevalence of histologic lesions were studied by immunofluorescence and histologic techniques. The findings showed no striking differences between dogs and cats. Antigen was found in the epithelia of the dorsal side of the tongue (96.3%), pharynx (81.0%), esophagus (50.0%), ventral side of the tongue (20.4%) and planum nasale (5.6%). The epithelia of the skin and the mucous membranes of the male and female genital organs never contained antigen. Moreover antigen was detected in the mucosa of the small intestine (85.2%), bone marrow (81.6%), spleen (79.6%), thymus (66.7%), mesenteric lymph nodes (60.4%), tonsilla palatina (58.5%), smooth muscle cells of the tunica muscularis of the small intestine (9.3%) and myocardium (1.9%). The histologic lesions found in intestinal mucosa, lymphatic tissues, bone marrow and myocardium are in accordance with literature. The tunica muscularis of the small intestine and the epithelium of tongue, pharynx and esophagus contained intranuclear inclusion bodies, the epithelium of tongue and pharynx showed necroses additionally. Tongue- and esophagus-erosions as well as -ulcers reported mainly in panleukopenia according to our results may be explained as a sequel of parvovirus infection of the epithelia of these organs. The prevalence of antigen and intranuclear inclusion bodies in the myocardium and smooth muscle cells of the small intestine--tissues with low or no mitotic activity,--allows to question the postulate of the parvoviruses' exclusive affinity to rapidly dividing cells.

Animals↗

[Molecular biological demonstration of parvovirus infection in fetal tissue].

We report on the morphological findings in 16 fetuses with serologically confirmed maternal parvovirus B19 infection. Typical routine morphological findings of the hydropic fetuses were the presence of abnormal erythroblasts with typical nuclear inclusions. These infected cells positively stained immunohistochemically with antibodies against a recombinant virus protein, as well as they ultrastructurally contained virus particles. Using in-situ hybridization techniques, we were able to demonstrate the presence of parvovirus B19 genome in the infected cells, while no other cell type was shown to contain virus genome. According to our results the differential diagnosis of fetal parvovirus B19 infection should be considered in each case with hydrops fetalis of unknown origin. The careful routine microscopic examination of fetal tissue may provide evidence for parvovirus infection which should be confirmed by in-situ hybridization analysis.

Bone Marrow↗

Inactivated canine parvovirus vaccines: an alternative method for assessment of potency.

Groups of three-week-old chickens were given graded doses of inactivated canine parvovirus vaccines. Blood samples were taken three weeks later and the sera examined by ELISA for antibodies to canine parvovirus. Reproducible, linear, log-dose serological responses were observed, enabling the potency of the vaccines to be compared. The simultaneous administration of other components of canine multivalent vaccines appeared to reduce the response to the parvovirus component. When its results have been correlated with the degree of protection in dogs this test could be used to assess the potency of inactivated canine parvovirus vaccines.

Animals↗

Parvovirus-like particles associated with diarrhea in unweaned piglets.

Numerous parvovirus-like particles, 18 to 26 nm in diameter, were detected by electron microscopy in the intestinal contents of two to three week old piglets with mild to severe diarrhea, in six Quebec pig herds. Hemagglutination of guinea pig and African green monkey red blood cells was obtained with clarified intestinal contents. Two isolates were found to be antigenically related to porcine and canine parvoviruses, while another differed from the porcine parvovirus using the hemagglutination-inhibition test. Three isolates could be cultivated in cell cultures as demonstrated by the development of a cytopathic effect, hemagglutination activity, immunofluorescence and identification of the virions in the cell culture fluids by electron microscopy. The possibility of a primary etiological role for these parvoviruses in diarrhea of unweaned piglets is discussed.

Animals↗

Parvovirus infection in children.

Human parvovirus, discovered fortuitously in 1975, is probably most often associated with an asymptomatic or mild nonspecific illness. This small DNA virus, like other members of the Parvoviridae, has a predeliction for rapidly growing cells, especially the erythroid precursor cells of bone marrow. The virus has now clearly been associated with specific clinical syndromes. Epidemiologic and experimental evidence clearly document human parvovirus as the etiologic agent of the acute aplastic crisis associated with various forms of chronic hemolytic anemia. It is also the etiologic agent of erythema infectiosum, the most frequent presentation of acute parvovirus infection in the normal child. The rash of erythema infectiosum is faint and evanescent and may not always be present or recognized, especially in black children. Frequently this infection may occur as a nonspecific viral syndrome in children or adults, accounting for the high incidence of seropositivity among adults despite an infrequent history of erythema infectiosum. The attack rate is highest among 7- to 10-year old contacts. Severe infection in the fetus has been associated with second trimester abortion. Persistent infection in an immunocompromised child has been associated with chronic aplasia of all marrow elements, suggesting the importance of a normal host immune system to contain this infection. The arthritis and arthralgia seen in older patients, especially women, occur after the viremia has ended, suggesting a possible immunologic pathogenesis for this complication. Volunteer studies have delineated the time course of the various manifestations of parvovirus infection. The ability to infect volunteers intranasally and the finding of virus in respiratory secretions suggests that this may be the route of spread to susceptible contacts.

Child↗

[Vascular purpura and other cardiovascular alterations in children with acute parvovirus B19 infection. Report of 3 personal cases].

Most frequent skin manifestation of parvovirus B19 infection is the erythema infectiosum (fifth disease; Sticker's disease). Vascular purpura (some cases of Henoch-Schönlein purpura) has been reported in virus infections such as infectious mononucleosis (Epstein-Barr virus), hepatitis B, cytomegalovirus etc., and human parvovirus B19 could be another cause. Clinical course, procedure of diagnostics and therapy in 3 own serologically established cases of vascular purpura or severe alterations of the blood circulation due to parvovirus B19 infection are presented. Parvovirus B19 (or other viruses) as a trigger for vascular purpura and alteration of the blood vessel wall and blood circulation could explain the childhood predominance and seasonal clustering of that disease. Furthermore an individual disposion (in form of special HLA type?) for the development of vascular purpura can be suggested.

Cardiovascular Diseases↗

Anti-DNA and antilymphocyte antibodies during acute infection with human parvovirus B19.

Sera from patients in the acute and recovery stages of parvovirus B19 infection, and from individuals with no detectable antiparvovirus antibody were examined for the presence of anti-DNA and antilymphocyte antibodies. Sixty-eight percent of individuals recently recovered from parvovirus infection had elevated levels of antidouble stranded (ds) and antisingle stranded (ss) DNA antibodies. In addition, a cytotoxic IgM antilymphocyte antibody was detected in more than 88% of these same sera. Serial specimens from volunteers experimentally infected with parvovirus B19 were also tested for these autoantibodies and it was determined that the presence of antilymphocyte IgM was dependent on the stage of infection. The antilymphocyte IgM was occasionally detectable in sera containing rubella specific IgM (11%) or varicella zoster specific IgM (25%). However, in contrast to B19 infection, these antibodies were not cytotoxic. From the results of our study, we propose that parvovirus infection of hematologically normal individuals may be accompanied by a transient, subclinical autoimmune state.

Antilymphocyte Serum↗