Effect of experimentally induced type II bovine viral diarrhea virus infection on platelet function in calves

OBJECTIVE: To evaluate platelet aggregation responses in calves experimentally infected with a thrombocytopenia-inducing type II bovine viral diarrhea virus (BVDV) isolate (BVDV 890). ANIMALS: 9 neonatal male Holstein calves. PROCEDURE: 5 calves were inoculated with BVDV 890, and 4 were used as controls. Platelet aggregation studies and attempts to isolate BVDV from platelets were performed 2 days before, the day of, and every 2 days for 12 days after inoculation. Platelet function was assessed by means of optical aggregometry, using adenosine diphosphate and platelet-activating factor as agonists. Bovine viral diarrhea virus was isolated from purified platelet preparations by use of an immunoperoxidase monolayer assay. RESULTS: Maximum percentage aggregation and slope of the aggregation curve decreased over time in calves infected with BVDV. Bovine viral diarrhea virus was not isolated from platelets from control calves, but it was isolated from infected calves from 4 through 12 days after inoculation. CONCLUSIONS AND CLINICAL RELEVANCE: Results suggest that platelet function may be depressed in calves infected with type II BVDV. Although the mechanism for altered platelet function was not determined, it likely involved an increase in the percentage of aged platelets in the circulation, a direct virus-platelet interaction, or an indirect virus-platelet interaction. Platelet dysfunction, in addition to thrombocytopenia, may contribute to the hemorrhagic syndrome associated with acute type II BVDV infection in calves.     

Platelet aggregation responses and virus isolation from platelets in calves experimentally infected with type I or type II bovine viral diarrhea virus.

Altered platelet function has been reported in calves experimentally infected with type II bovine viral diarrhea virus (BVDV). The purpose of the present study was to further evaluate the ability of BVDV isolates to alter platelet function and to examine for the presence of a virus-platelet interaction during BVDV infection. Colostrum-deprived Holstein calves were obtained immediately after birth, housed in isolation, and assigned to 1 of 4 groups (1 control and 3 treatment groups). Control calves (n = 4) were sham inoculated, while calves in the infected groups (n = 4 for each group) were inoculated by intranasal instillation with 10(7) TCID50 of either BVDV 890 (type II), BVDV 7937 (type II), or BVDV TGAN (type I). Whole blood was collected prior to inoculation (day 0) and on days 4, 6, 8, 10, and 12 after inoculation for platelet function testing by optical aggregometry by using adenosine diphosphate and platelet activating factor. The maximum percentage aggregation and the slope of the aggregation curve decreased over time in BVDV-infected calves; however, statistically significant differences (Freidman repeated measures ANOVA on ranks, P < 0.05) were only observed in calves infected with the type II BVDV isolates. Bovine viral diarrhea virus was not isolated from control calves, but was isolated from all calves infected with both type II BVDV isolates from days 4 through 12 after inoculation. In calves infected with type I BVDV, virus was isolated from 1 of 4 calves on days 4 and 12 after inoculation and from all calves on days 6 and 8 after inoculation. Altered platelet function was observed in calves infected with both type II BVDV isolates, but was not observed in calves infected with type I BVDV. Altered platelet function may be important as a difference in virulence between type I and type II BVDV infection.     

Thrombocytopenia and hemorrhages in veal calves infected with bovine viral diarrhea virus

The relationship between bovine viral diarrhea virus (BVDV) infection and thrombocytopenia was studied in 18 veal calves experimentally infected with BVDV. All calves were free of BVDV, and 13 calves were free of serum neutralizing antibodies to BVDV before virus inoculation. Calves were inoculated at approximately 10 days of age, and platelet counts were monitored over a period of several weeks. Ten additional calves housed in close proximity were kept as uninoculated controls. A profound decrease in platelet counts by 3 to 11 days after inoculation was seen in all calves that had neutralizing antibody titers less than 1:32 before infection. Severe thrombocytopenia (less than 5,000 platelets/microliter) was seen in 12 calves, 11 of which also developed hemorrhages. Necropsy findings in 3 severely thrombocytopenic calves that died included multiple hemorrhages throughout the body. Calves that recovered had increased platelet counts, and in most instances, a corresponding increase in neutralizing antibody titers to BVDV. At 11 days after inoculation, BVDV was detected on platelets by use of immunofluorescence, but evidence of surface-bound immunoglobulin was not found. The results suggest that a nonimmunoglobulin-mediated method of platelet destruction or sequestration develops as a sequela to BVDV infection.     

Experimental model of type II bovine viral diarrhea virus-induced thrombocytopenia in neonatal calves.

Thrombocytopenia has been associated with type II bovine viral diarrhea virus (BVDV) infection in immunocompetent cattle, but the mechanism is unknown. The purpose of the present study was to develop and characterize a model of type II BVDV-induced thrombocytopenia. Colostrum-deprived Holstein calves were obtained immediately after birth, given a BVDV-negative and BVDV antibody-negative plasma transfusion, housed in an isolation facility, and randomly assigned to either control (n = 4) or infected (n = 5) groups. Infected calves were inoculated by intranasal instillation on day 3 of age with 10(7) TCID50 of the prototype type II isolate, BVDV 890, whereas control calves were sham inoculated. Blood counts and virus isolations from serum, white blood cells, and platelets were performed daily until day 12 after infection, at which time all experimental calves were euthanatized, and pathologic, virologic, and immunohistochemical examinations were performed. On physical examination, the control calves remained normal, but the infected calves developed pyrexia and diarrhea characteristic of type II BVDV infection. The platelet count decreased in all infected calves, and a statistically significant difference in the platelet count between control and infected calves was observed on days 7-12 after infection. In addition, the mean platelet volume and white blood cell counts also decreased. Examination of the bone marrow from the infected calves revealed immunohistochemical staining for BVDV antigen in megakaryocytes and evidence of concurrent megakaryocyte necrosis and hyperplasia.     

Evaluation of transmission of bovine viral diarrhea virus (BVDV) between persistently infected and naive cattle by the horn fly <Emphasis Type="Italic">(Haematobia irritans)</Emphasis>

Identifying reservoirs and transmission routes for bovine viral diarrhea virus (BVDV) are important in developing biosecurity programs. The aim of this study was to evaluate BVDV transmission by the hematophagous horn fly (Haematobia irritans). Flies collected from four persistently infected cattle were placed in fly cages attached to principal (n?=?4) and control (n?=?4) BVDV-naïve calves housed individually in isolation rooms. Flies were able to feed on principal calves, but a barrier prevented fly feeding from control calves. Flies were tested for BVDV by RT-PCR and virus isolation at time of collection from PI cattle and after 48 h of exposure on BVDV-naïve calves. Blood samples were collected from calves and tested for BVDV infection. Virus was isolated from fly homogenates at collection from PI animals and at removal from control and principal calves. All calves remained negative for BVDV by virus isolation and serology throughout the study. Bovine viral diarrhea virus may be detected in horn flies collected from PI cattle, but horn flies do not appear to be an important vector for BVDV transmission.     

Serologic evaluation of five unvaccinated heifers to detect herds that have cattle persistently infected with bovine viral diarrhea virus

OBJECTIVE: To determine whether serologic evaluation of 5 unvaccinated 6- to 12-month-old heifers is a valid method for identifying herds that contain cattle persistently infected (PI) with bovine viral diarrhea virus (BVDV). ANIMALS: 14 dairy herds with a history of BVDV infection, with health problems consistent with BVDV infection, or at risk for contracting BVDV infection. PROCEDURE: 5 unvaccinated 6- to 12-month-old heifers were randomly selected from each herd. Neutralizing antibody titers for type-I and -II BVDV were determined. A herd was classified as likely to contain PI cattle when at least 3/5 heifers had antibody titers > or = 128. Virus isolation was performed on all cattle to identify PI cattle. Genotype of isolated viruses was determined by nested multiplex polymerase chain reaction. RESULTS: 6 of 14 herds contained PI cattle. Sensitivity and specificity of serologic evaluation of 5 heifers for identifying these herds were 66 and 100%, respectively. In herds that contained PI cattle, the predominant BVDV titer in the tested heifers corresponded to the genotype of the isolated virus. CONCLUSIONS AND CLINICAL RELEVANCE: Serologic evaluation of unvaccinated 6- to 12- month-old heifers is an accurate method for identifying herds containing PI cattle. Both type-I and -II BVDV antibody titers should be determined to prevent herd misclassification. The genotype of BVDV found in PI cattle can be predicted by the predominant neutralizing antibody titers found in tested heifers. Serologic evaluation of 5 unvaccinated heifers can be used to determine whether a herd is likely to contain PI cattle.     

Transmission of Bovine viral diarrhea virus 1b to susceptible and vaccinated calves by exposure to persistently infected calves

Bovine viral diarrhea virus (BVDV) persistently infected (PI) calves represent significant sources of infection to susceptible cattle. The objectives of this study were to determine if PI calves transmitted infection to vaccinated and unvaccinated calves, to determine if BVDV vaccine strains could be differentiated from the PI field strains by subtyping molecular techniques, and if there were different rates of recovery from peripheral blood leukocytes (PBL) versus serums for acutely infected calves. Calves PI with BVDV1b were placed in pens with nonvaccinated and vaccinated calves for 35 d. Peripheral blood leukocytes, serums, and nasal swabs were collected for viral isolation and serology. In addition, transmission of Bovine herpes virus 1 (BHV-1), Parainfluenza-3 virus (PI-3V), and Bovine respiratory syncytial virus (BRSV) was monitored during the 35 d observation period. Bovine viral diarrhea virus subtype 1b was transmitted to both vaccinated and nonvaccinated calves, including BVDV1b seronegative and seropositive calves, after exposure to PI calves. There was evidence of transmission by viral isolation from PBL, nasal swabs, or both, and seroconversions to BVDV1b. For the unvaccinated calves, 83.2% seroconverted to BVDV1b. The high level of transmission by PI calves is illustrated by seroconversion rates of nonvaccinated calves in individual pens: 70% to 100% seroconversion to the BVDV1b. Bovine viral diarrhea virus was isolated from 45 out of 202 calves in this study. These included BVDV1b in ranch and order buyer (OB) calves, plus BVDV strains identified as vaccinal strains that were in modified live virus (MLV) vaccines given to half the OB calves 3 d prior to the study. The BVDV1b isolates in exposed calves were detected between collection days 7 and 21 after exposure to PI calves. Bovine viral diarrhea virus was recovered more frequently from PBL than serum in acutely infected calves. Bovine viral diarrhea virus was also isolated from the lungs of 2 of 7 calves that were dying with pulmonary lesions. Two of the calves dying with pneumonic lesions in the study had been BVDV1b viremic prior to death. Bovine viral diarrhea virus 1b was isolated from both calves that received the killed or MLV vaccines. There were cytopathic (CP) strains isolated from MLV vaccinated calves during the same time frame as the BVDV1b isolations. These viruses were typed by polymerase chain reaction (PCR) and genetic sequencing, and most CP were confirmed as vaccinal origin. A BVDV2 NCP strain was found in only 1 OB calf, on multiple collections, and the calf seroconverted to BVDV2. This virus was not identical to the BVDV2 CP 296 vaccine strain. The use of subtyping is required to differentiate vaccinal strains from the field strains. This study detected 2 different vaccine strains, the BVDV1b in PI calves and infected contact calves, and a heterologous BVDV2 subtype brought in as an acutely infected calf. The MLV vaccination, with BVDV1a and BVDV2 components, administered 3 d prior to exposure to PI calves did not protect 100% against BVDV1b viremias or nasal shedding. There were other agents associated with the bovine respiratory disease signs and lesions in this study including Mannheimia haemolytica, Mycoplasma spp., PI-3V, BRSV, and BHV-1.     

Multiple diagnostic tests to identify cattle with Bovine viral diarrhea virus and duration of positive test results in persistently infected cattle

Several tests for Bovine viral diarrhea virus (BVDV) were applied to samples collected monthly from December 20, 2005, through November 27, 2006 (day 0 to day 342) from 12 persistently infected (PI) cattle with BVDV subtypes found in US cattle: BVDV-1a, BVDV-1b, and BVDV-2a. The samples included clotted blood for serum, nasal swabs, and fresh and formalin-fixed ear notches. The tests were as follows: titration of infectious virus in serum and nasal swabs; antigen-capture (AC) enzyme-linked immunosorbent assay (ELISA), or ACE, on serum, nasal swabs, and fresh ear notches; gel-based polymerase chain reaction (PCR) testing of serum, nasal swabs, and fresh ear notches; immunohistochemical (IHC) testing of formalin-fixed ear notches; and serologic testing for BVDV antibodies in serum. Of the 12 animals starting the study, 3 died with mucosal disease. The ACE and IHC tests on ear notches had positive results throughout the study, as did the ACE and PCR tests on serum. There was detectable virus in nasal swabs from all the cattle throughout the study except for a few samples that were toxic to cell cultures. The serum had a virus titer ≥ log₁₀ 1.60 in all samples from all the cattle except for 3 collections from 1 animal. Although there were several equivocal results, the PCR test most often had positive results. The BVDV antibodies were due to vaccination or exposure to heterologous strains and did not appear to interfere with any BVDV test. These findings illustrate that PI cattle may be identified by several tests, but differentiation of PI cattle from cattle with acute BVDV infection requires additional testing, especially of blood samples and nasal swabs positive on initial testing. Also, calves PI with BVDV are continual shedders of infectious virus, as shown by the infectivity of nasal swabs over the 11-mo study.     

Persistent infections after natural transmission of bovine viral diarrhoea virus from cattle to goats and among goats

Bovine viral diarrhoea virus (BVDV) is an economically important pathogen of cattle worldwide. Infection of a pregnant animal may lead to persistent infection of the foetus and birth of a persistently infected (PI) calf that sheds the virus throughout its life. However, BVD viruses are not strictly species specific. BVDV has been isolated from many domesticated and wild ruminants. This is of practical importance as virus reservoirs in non-bovine hosts may hamper BVDV control in cattle. A goat given as a social companion to a BVDV PI calf gave birth to a PI goat kid. In order to test if goat to goat infections were possible, seronegative pregnant goats were exposed to the PI goat. In parallel, seronegative pregnant goats were kept together with the PI calf. Only the goat to goat transmission resulted in the birth of a next generation of BVDV PI kids whereas all goats kept together with the PI calf aborted. To our knowledge, this is the first report which shows that a PI goat cannot only transmit BVD virus to other goats but that such transmission may indeed lead to the birth of a second generation of PI goats. Genetic analyses indicated that establishment in the new host species may be associated with step-wise adaptations in the viral genome. Thus, goats have the potential to be a reservoir for BVDV. However, the PI goats showed growth retardation and anaemia and their survival under natural conditions remains questionable.     

Amplification of Bovine Viral Diarrhoea Virus Introduced into an In Vitro Embryo Production System Via Oocytes from Persistently Infected Cattle

The purpose of this study was to determine whether or not embryos derived from in vitro fertilization of oocytes from persistently infected (PI) cattle would contain infectious virus. Three in vitro embryo production treatment groups were assessed: 1) oocytes and uterine tubal cells (UTC) free of bovine viral diarrhoea virus (BVDV) (negative control), 2) oocytes free of BVDV fertilized and cultured in media containing UTC obtained from PI heifers, and 3) oocytes from PI heifers fertilized and cultured in media containing UTC free of BVDV. The developmental media, UTC and embryos (individual or groups of five) were assayed for virus. Virus was not isolated from any samples in treatment group 1. As shown in previous studies, a proportion of embryo samples were positive for BVDV in treatment group 2. In treatment group 3, the virus associated with the oocytes contaminated the developmental media and infected susceptible co-culture cells used during fertilization and culture. In addition, 65% (11/17) of the degenerated ova from treatment group 3 had infectious virus associated with them. While none of the ova developed into transferable embryos, the study did confirm that use of oocytes from PI cows could lead to amplification of BVDV and cross contamination during in vitro embryo production.     

Evaluation of two commercial enzyme-linked immunosorbent assays for detection of bovine viral diarrhoea virus in serum and skin biopsies of cattle

AIM: To assess the ability of two commercial bovine viral diarrhoea (BVD) virus (BVDV) antigen-capture enzyme-linked immunosorbent assays (ELISAs) to detect virus in serum and skin biopsies. METHODS: Thirty cattle persistently infected (PI) with BVDV were identified using routine diagnostic laboratory testing. Additional ear-notch skin biopsies and blood samples were collected from these animals to confirm the diagnosis, and from 246 cohorts, to determine their BVDV status. Skin biopsies were soaked overnight in buffer and the eluate collected. All sera and eluate were tested using two commercially available ELISAs for detecting BVDV antigen, and a subsample of positive and negative sera was tested using a polymerase chain reaction (PCR) test. A study was also performed to ascertain the risk of cross contamination occurring during the collection and processing of skin biopsies. RESULTS: Both serum and skin samples tested using either ELISA resulted in the detection of all cattle identified as PI and no non-infected cattle were incorrectly classified as infected using either method. Agreement between all assays (ELISAs, whether performed on serum or skin, and PCR) was 100%. No cross-contamination of skin samples between animals was evident using routine biopsy methods. CONCLUSIONS: Viraemic cattle infected with BVDV were accurately identified using either of the two commercial ELISAs evaluated on either serum or skin samples. CLINICAL RELEVANCE: Either skin biopsies or serum samples can be collected from cattle to determine their BVDV status. This should overcome problems in accurately identifying the infection status of young calves in which colostral antibodies might interfere with the antigen-capture ELISA.     

牛病毒性腹泻病毒JN株的分离鉴定及E2基因的序列分析

本研究从疑似牛病毒性腹泻病毒(bovine viral diarrhea virus,BVDV)感染牛的分泌物与排泄物中分离鉴定1株牛病毒性腹泻病毒,并进行E2基因序列分析。结果表明,分离株病毒命名为JN株;Reed-Muench法测定分离株病毒TCID₅₀为10^-7.5/0.1 mL;病毒中和试验结果表明,BVDV JN分离株可被BVDV阳性血清特异性中和,而不能被BVDV阴性血清中和;分离株病毒E2基因序列测序结果表明,该分离毒株属于BVDVⅠa亚型。     

Experimental persistent infection with bovine viral diarrhea virus in white-tailed deer

Bovine viral diarrhea virus (BVDV) infections cause substantial economic losses to the cattle industries. Persistently infected (PI) cattle are the most important reservoir for BVDV. White-tailed deer (Odocoileus virginianus) are the most abundant species of wild ruminants in the United States and contact between cattle and deer is common. If the outcome of fetal infection of white-tailed deer is similar to cattle, PI white-tailed deer may pose a threat to BVDV control programs. The objective of this study was to determine if experimental infection of pregnant white-tailed deer with BVDV would result in the birth of PI offspring. Nine female and one male white-tailed deer were captured and housed at a captive deer isolation facility. After natural mating had occurred, all does were inoculated intranasally at approximately 50 days of pregnancy with 10(6) CCID(50) each of a BVDV 1 (BJ) and BVDV 2 (PA131) strain. Although no clinical signs of BVDV infection were observed or abortions detected, only one pregnancy advanced to term. On day 167 post-inoculation, one doe delivered a live fawn and a mummified fetus. The fawn was translocated to an isolation facility to be hand-raised. The fawn was determined to be PI with BVDV 2 by serial virus isolation from serum and white blood cells, immunohistochemistry on skin biopsy, and RT-PCR. This is the first report of persistent infection of white-tailed deer with BVDV. Further research is needed to assess the impact of PI white-tailed deer on BVDV control programs in cattle.     

Analysis of variation of bovine viral diarrhoea virus E2 sequence following transplacental infection of cattle

The genetic and antigenic diversity observed in field isolates of bovine viral diarrhoea virus (BVDV) is thought to occur during acute infection because of the genetic stability observed in BVDV throughout the lifetime of persistently infected (PI) cattle. In this study, 15 cows in early pregnancy were inoculated with identical challenge doses obtained from a single infectious inoculum of the virologically cloned isolate Pe515nc. In order to examine the diversity that may develop in utero in the PI foetus, the variable E2 sequence of the virus isolated directly from the serum of each PI calf was compared. A high degree of sequence similarity was demonstrated, with 0-4 nucleotide differences out of 608 bases compared. Thus, the virus showed relatively few genomic changes in any of the PI calves, although we observed that the in utero environment did provide some opportunity for genetic variation to become established.     

Study of cattle persistently infected with bovine viral diarrhea virus that lack detectable virus in serum

OBJECTIVE: To determine whether cattle persistently infected with bovine viral diarrhea virus (BVDV) that lack virus detectable in serum by use of the immunoperoxidase microtiter assay (IPMA) can transmit the virus to susceptible herdmates and determine prevalence of these cattle. DESIGN: Clinical trial and serologic survey. SAMPLE POPULATION: 2 cattle and 1,952 blood samples. PROCEDURE: A persistently infected cow in which virus could not be detected in serum was housed with a BVDV-seronegative steer. Blood and nasal swab specimens were tested via virus isolation and serum virus neutralization. Parallel WBC preparations and sera from blood samples of 1,952 adult cows were screened for BVDV by use of IPMA. RESULTS: The steer seroconverted to BVDV within 4 weeks of contact with the cow. Virus was detected in sera and WBC of 5 adult cows that were verified as persistently infected by retest 3 weeks later. Cattle persistently infected with BVDV in which virus could not be detected in both serum and WBC by use of IPMA were not found. CONCLUSION AND CLINICAL RELEVANCE: Cattle persistently infected with BVDV in which virus cannot be detected in serum by use of IPMA may serve as virus reservoirs for infecting susceptible cattle. Persistent infection was detected at a prevalence of 0.26%. Screening adult cattle by use of IPMA on serum samples appears to be a reliable means of detecting persistent infection with BVDV. Prevalence of cattle persistently infected with BVDV that have negative results of IPMA on serum is extremely low.     

Field application of the combination of neutralizing test and virus isolation, so-called spot test, to detect herds including cattle persistently infected with bovine viral diarrhea virus

To detect herds including cattle persistently infected (PI) with bovine viral diarrhea virus (BVDV), application of the combination of neutralizing antibody detection and virus isolation, so-called spot test, were performed on sera of 3 calves selected from each of 26 farms. Nine farms were judged as positive because 64 or more antibody titers were detected from 2 or more calves or BVDV was isolated from one or more calves. PI cattle were detected from 8 of the 9 farms. The positive judgment on one farm was obtained only when the indicator virus used on the neutralizing test was genotypically identical with the isolate from the farm. These results suggest that the spot test can be effective in detecting herds with PI cattle and that the accuracy may be influenced by the genotypes of the indicator viruses.     

Immunohistochemistry used as a screening method for persistent bovine viral diarrhea virus infection.

Cattle persistently infected (PI) with bovine viral diarrhea virus(BVDV) are a major source of infection to herds. To successfully control BVDV, it is necessary to identify and cull those cattle PI with BVDV. Immunohistochemistry (IHC) is a useful tool for sensitive and specific detection of BVDV antigens in infected cattle.Skin of cattle PI with BVDV is one of the tissues where BVDV can be consistently identified by IHC and is readily accessible for sampling. Use of IHC on skin biopsies (in the form of ear notches)as a method to identify cattle PI with BVDV has resulted in a reliable, affordable technique for mass testing of cattle at an early age without maternal antibody interference. The ability to test large numbers of cattle to identify those Pl with BVDV will enable implementation of programs for control and eventual eradication of BVDV.     

Inactivation at various temperatures of bovine viral diarrhea virus in beef derived from persistently infected cattle

Bovine viral diarrhea virus (BVDV) is a pestivirus that is enzootic in most cattle populations throughout the world. This virus is present throughout the body of persistently infected (PI) cattle. Previous research has not assessed the cooking temperature at which BVDV in meat from PI cattle can be inactivated. Therefore, muscle tissue from 6 PI cattle was harvested, refrigerated, frozen, and heated to various internal temperatures. The concentration of virus present was determined by virus isolation. Average cell culture infective doses (50% endpoint; CCID(50)) of BVDV per gram of frozen, uncooked meat from PI cattle were 10(5.85) CCID(50)/g of whole cuts and 10(6.02) CCID(50)/g of ground meat. The virus in whole and ground meat was consistently inactivated when cooked to temperatures greater than or equal to 75°C. A second objective of this research was to thoroughly reassess if Vero cells were permissive to BVDV infection in our laboratory to provide further indication of whether primates, including humans, might be susceptible to BVDV. Vero cells were not permissive to infection with any of 43 different strains of BVDV that readily replicated in Madin Darby bovine kidney cells. In conclusion, this bovine pathogen, which is not considered to be a human pathogen, can be inactivated by cooking ground or whole cuts of meat to 75°C or higher. Care should be taken to ensure that susceptible hosts such as pigs are not fed improperly cooked meat, meat by-products, or waste food originating from PI cattle.     

Distribution of viral antigen and tissue lesions in persistent and acute infection with the homologous strain of noncytopathic bovine viral diarrhea virus.

Viral distribution and lesions were compared between calves born with persistent infection (PI) and calves acutely infected with the same bovine viral diarrhea virus (BVDV) isolate. Two PI calves from 1 dairy herd were necropsied. The PI viruses from these calves were isolated, characterized by sequencing, and found to be identical. This virus strain, designated BVDV2-RS886, was characterized as a noncytopathic (ncp) type 2 BVDV. To establish acute infections, BVDV2-RS886 was used to inoculate clinically healthy, seronegative calves which were 3 weeks to 3 months old. Nine calves received 10(6)-10(7) tissue culture infective dose of BVDV2-RS886 intranasally. Four additional age-matched animals served as noninfected controls. Infected calves were necropsied at 3, 6, 9, or 13 days postinoculation (dpi). Viral antigen was detected by immunohistochemistry in frozen sections, and lesions were evaluated in hematoxylin eosin-stained paraplast sections. In the PI calves, a wide distribution of viral antigen was found in all tissues and was not associated with lesions. In the acutely infected calves, viral antigen was widespread in lymphoid tissues at 6 dpi but had been mostly eliminated at 9 and 13 dpi. Depletion of lymphoid tissues was seen at 6, 9, and 13 dpi and repopulation at 9 and 13 dpi. In 1 of the calves at 13 dpi, severe arteritis was present in lymph nodes and myocardium. This comparison shows that an ncp BVDV strain that causes no lesions in PI animals is able to induce marked depletion of lymphoid tissues in calves with acute infection. Therefore, the failure to eliminate PI cattle from a herd causes problems not only in pregnant cattle but may also affect other age groups.