Bovine respiratory syncytial virus (BRSV) infects many types of epithelial cells in both the upper and lower respiratory tracts, including tonsilar epithelium. In humans, HRSV is considered one of the “common cold” viruses in older children, adolescents and adults. It is likely that the same thing occurs in cattle with BRSV infections explains John Ellis, DVM, PhD, Dipl. ACVP, Dipl. ACVM, Western College of Veterinary Medicine, University of Saskatchewan.

In a pure RSV infection you have what could be called an upstairs/downstairs lung. “You have an anterior-ventral atelectasis and dorsally you have either emphysema, interlobular emphysema or even subcutaneous emphysema when you get rupture of some of the alveoli,” Ellis says. “You can often see big bullae but you might not always. You may just see interstitial emphysema. It’s pretty dramatic and pretty characteristic. Interestingly, you don’t seem to see that degree of emphysema with a pure PI3V infection.”

Shawn Blood, DVM, Hitch Consulting Service, Guymon, Okla., says the emphysema is the most profound thing he and his feedyard technicians see on a postmortem exam. “Most of the routine postmortem exams on cattle that die with respiratory disease are typical Mannheimia pneumonias; it would be the one that rises to the top and what our technicians and I see the most.”

Ellis agrees and says from a teaching perspective maybe that’s part of the confusion. “In virtually every dead feedlot animal we see there are going to be multiple agents involved, so it’s hard to implicate any one, BRSV in particular. It becomes really difficult. I think anytime you get bronchial constriction, whether it is because there is debris in there or whether you get hyperresponsiveness of the airways, you’re going to have a tendency to get that emphysema. In fact, cattle are prone to develop emphysema because they have poor collateral ventilation in the lung.”

How BRSV works

Unlike some other viruses, Ellis says it’s rare to have viremia with either BRSV or parainfluenza-3 virus (PI3V). “The reason is where the virus replicates and also where it buds,” he explains. “It buds from the apical surface, so it doesn’t really have a chance to get into the circulation, whereas herpes viruses bud from the basal lateral surfaces as well, as does bovine viral diarrhea virus (BVDV), so that gives those viruses a chance to get beyond the basement membrane and into the circulation, then you get viremia.”

Ellis says immunosuppressed individuals can have viremia with RSV, which is documented in humans, and PI3V as well, but that probably doesn’t happen that often in cattle. “The thing about viremia is it’s generally going to be with systemic infections like bovine herpesvirus-1 (BHV-1) and BVDV that have a viremic phase, and not something that just infects the respiratory epithelium and buds from the apical surface.”

Ellis says probably most of the budding that occurs is non-cytopathic. “It’s only at the end of the infection in the individual cell that you get death of the cell, and that makes sense from the virus’ perspective,” he says. “You don’t want to be killing the cell you’re living in too early.” That tends to happen maybe four to five days after infection.

It’s not clear, however, how those cells actually die. Ellis notes that it used to be that cells died by either necrosis or apoptosis. Now there’s many more pathways recognized as to how cells die. “It turns out that most viruses, including BRSV and PI3V, have anti-apoptic mechanisms which prevent the death of the cell, which makes a lot of sense from the virus’ perspective,” he says. “You want to prolong the life of the cell you’re replicating in and increase the number of progeny you have. It’s pretty complicated at the cellular level and we don’t really understand completely what’s going on, with any of these viruses, in terms of the interactions between the virus and the cell.”

BRSV damages the respiratory epithelium. Ellis says it’s controversial whether it’s from
necrosis and apoptois, but there’s direct damage to the mucociliary escalator, setting animals up for secondary bacterial infection. The airways are disrupted because of the virus and there is a dramatic expiratory dyspnea because of the clogging of airways with dead epithelial cells and inflammatory debris. “That’s what leads to the dramatic expiratory dyspnea with BRSV that doesn’t seem to be as dramatic with PI3V,” Ellis says.

BRSV targets naïve cattle

Calvin Booker, DVM, Feedlot Health Management Services, Okotoks, Alberta, says there are two main populations where he sees BRSV. “One factor is age or some proxy of age which is probably size/body weight,” he says. “I think if they’re lighter we’re more likely to see disease with BRSV. But in older populations or bigger populations, if they’re naïve populations coming in, they’re probably as susceptible as anything because they’ve never been to town before; they’ve never seen the virus.”

Kelly Lechtenberg, DVM, PhD, Midwest Veterinary Services, Oakland, Neb., sees the same thing. “Where we’ve seen our most severe clinical effects are in big, naïve cattle that have come off of grass into the feedyards. Our experience a couple of different times has been that naïve groups of cattle come in, get exposed, get stressed and crash.”

Two cases that stick out in his mind were in the same feedyard. Cattle arrived during very hot weather in July or August. “I believe that we had some of the cattle shedding the virus and conditions of cattle grouping closely together under sprinkler systems combined with extremely high respiratory rates contributed to a viral epidemic. I didn’t think too much about this until we had a second case that was very similar.”

Blood has not seen much BRSV in his Oklahoma feedyards, but he used to see quite a bit of it in Nebraska. “We saw some on nursing calves in the summertime. The guys call it summer pneumonia in calves. We saw some in the feedyard, but I haven’t seen it in big yearling cattle as some of the others have described. In general, I’ve seen it more in younger or smaller animals.”

Blood adds that in the Oklahoma Panhandle and Kansas, he doesn’t have many situations where naïve yearlings are coming in. “The cattle that we typically receive have had several incidences where they’ve been commingled with other cattle over their lifetime,” he says. “To have a population of naïve yearlings would be rare for us.”

Naivety seems to be the key, says Dan Givens, DVM, PhD, Auburn University. “It’s interesting how, sometimes unintentionally, ‘good management’ without strategic vaccination or serendipitous exposure to viruses can set up more of a train wreck than management that involves some commingling where calves develop natural immunity because of the groups that they’ve been exposed to. So, we’ve seen a couple of situations where well-intentioned management that lacked strategic vaccination would result in naïve calves that can really be problematic when the virus gets into the group of calves and then disseminates within the group to cause problems.”

From infection to clinical signs

From an experimental standpoint, Ellis has seen clinical signs of BRSV as early as three days after challenge, and severe clinical signs usually five days after challenge. Booker agrees and says if you go back and look at situations where BRSV outbreaks have occurred in some naive populations, they usually don’t happen the day that the cattle arrive. “It’s usually some time near the end of the first week when you start to see clinical signs of BRSV, or maybe even two weeks at times,” Booker says. “So that probably fits with exposure post-feedlot followed by a time period for the virus to both replicate within individual animals and spread within the population.”

Booker says the outbreaks usually last two or three days, “But that’s usually because, as opposed to just counting the sick ones and the dead ones, we usually try to step in and mass medicate. I’m not sure we’re accomplishing anything that wouldn’t happen if we left them alone or not.”

Lechtenberg says in challenge models he starts to see a pretty significant virus shedding by day three, with temperature increases and some respiratory distress at five to seven days post-challenge, which last about five to seven days. “In a clinical situation, onset would be less predictable because you never really know the exposure pattern,” he explains. “Usually I expect onset within the first two weeks of arrival. The duration will spread out also, since susceptible cattle are not all exposed at the same time. New cases are generally recognized for several days. We usually intervene with modified-live vaccination once we figure out what’s going on.”

When dealing the BRSV-infected cattle, Lechtenberg hears cowboys describe the cattle more in terms of “respiratory character” than “depression”, which is typically associated with most BRD cases. “I used to have a bias that a lot of the depression we saw was due to fever and that the cattle were showing signs of depression because they had elevated temperatures. Now I believe that most of the depression we see is seemingly related to bacterial components of BRD and the associated toxemia and immune response related to the bacterial infection.”

Lechtenberg conducts several viral challenge studies every year and says it’s interesting to observe a specific viral infection without confounding factors of other viruses, other bacteria or environmental stressors that are usually present in most clinical feedlot cases. “Based our experience, BHV-1 and BRSV are really prime examples of pathogens (especially BHV-1) that cause cattle to elicit a very strong febrile response and at the same time only minimal clinical depression. The cowboys would say that cattle look pretty darn good for being ‘that hot’. These are the type of cattle that a cowboy will ride past today and make a mental note to himself and say ‘I want to see that calf again tomorrow’.”

Lechtenberg says if that calf was pulled, put in the chute and temped, they might find that he is running 106–107°F and might be a little off feed that day. He might have dropped a few pounds, have a serous nasal discharge and the eyes might be a little bit watery.

Compared to BHV-1, Lechtenberg says both viral infections take a little time to clear. “In both cases, most calves will look better several days later. BRSV calves will clinically recover quicker than BHV-1 calves. In addition to lung pathology, the BHV-1 cattle also need to heal the upper respiratory tract and repair the clearance mechanism and are more prone to secondary bacterial infections.”

Booker has had similar experiences and says when you have a clinical outbreak of BRSV and a clinical outbreak of BHV-1, the clinical outbreak of BRSV ends much sooner and the cattle look better very quickly once it stops. “BHV-1 drags on forever and probably part of that is because of all the secondary bacterial infections that occur. It can take weeks or months to clear up a BHV-1 outbreak. If it’s a true BHV-1 outbreak with clinical disease in the pen, it takes a long time to clear it up. With BRSV, a few days to a week later, they don’t look like the same cattle.”

Calves and BRSV

“Summer pneumonia” of beef calves is caused by BRSV, but how it circulates through the cowherd can be confusing. Ellis says most of the adults can have repeated infections, and there can even be subclinical infection at some level. “I think you can have subclinical infection with most respiratory pathogens,” Ellis says. “With herpes virus such as BHV-1, it’s different because there’s actually a latent infection when you’re not expressing many of the genes and then at some point the infection recrudesces or comes back with replication of the virus, which is very different from the situation with BRSV and other viruses. They don’t hide out in neurons and not express their genes. It’s a very different scenario.”

The term “summer pneumonia”, however, is really a misnomer, says Ellis. “It often happens in the summer but, but it coincides when the maternal antibodies are gone. I think it probably doesn’t have that much to do with it being summer.”

“It’s the timing of the maternal antibodies in the spring calving herd,” adds Givens. “The duration of maternal immunity against BRSV is relatively short. It all depends on the initial antibody titer in the calf to determine when the calf becomes susceptible.”

It doesn’t really matter what the specificity of the colostral antibodies is for, notes Ellis. “They are all going to fall off at a set interval; about a three-week half-life for IgG in the absence of infection.”

Do calves have more of one antibody than another from maternal immunity? Ellis doesn’t think at an individual antibody molecule level it matters what the specificity is. “If it’s an IgG molecule it’s going to decay at a given rate, in the absence of infection or ‘using it up’. It’s poorly documented, but an active infection probably depletes the antibody specific to it, which would effectively decrease the half-life. So in the case of a BVDV, maybe you generally have higher titers in cows that are passed to calves, so it’s a ‘more is better’ type of thing.”

Givens says that perhaps, as that calf loses the BHV-1 titer from maternal antibodies, there might be enough recrudescence in the herd that there’s exposure at the right time and just as the maternal antibodies are declining, the calf is exposed, resulting in immunity rather than disease. “In contrast, BRSV maternal antibodies decline but there’s not that low level of exposure, so finally when it does reappear with the long-term or prolonged infection, we’re not sure how it gets entry. Then you get a situation where you truly have a naive calf and get disease. But a lot of that is hypothetical.”

Ellis believes that most calves, and most human babies, are going to be exposed to RSV while they have maternal antibodies. “That’s the reason why most kids don’t have clinical RSV even though the virus is all over the place. The virus is all over the place in the human population but very few kids are hospitalized for it. Subclinical endemic infection is free vaccination for young animals. When that occurs in the face of maternal antibodies that’s nature’s way of protecting the population.”

Whether it’s bovine or human RSV, it’s an endemic virus. Most kids are probably exposed while they have maternal antibodies; they’re primed effectively, Ellis says. The RSV disease in humans and cattle doesn’t get sequentially worse, which would be hypersensitivity, it gets sequentially less severe because you have a better immune response, a more mature immune response.

“This is completely opposite of the hypersensitivity idea, because you tend to get worse upon re-exposure, or at least not better if you are hypersensitive to something,” Ellis explains. “The whole hypersensitivity thing conveys the wrong idea. You just look at the population level and it can’t be right because otherwise most cattle would be having hypersensitivity reactions because the virus is all over the place.” He adds that just because a 2-month old calf with clinical signs and BRSV might die, it’s probably a naïve calf and very susceptible to BRSV, but it doesn’t necessarily mean it had hypersensitivity.

But how does the BRSV get into the cowherd in the first place? Both of the paramyxoviruses, BRSV and PI3V, are endemic, and “Most individuals have free vaccination and don’t ever get sick,” Ellis says. “So, we only see the tip of the iceberg of those that haven’t been exposed when they had maternal antibodies. That’s a hypothesis but I think that explains the epidemiology. We focus on the sick animals, which is a minority.”

Booker and Ellis make the parallel between calves to sending kids to kindergarten. “Whether it be kids or calves, you want some combination of free vaccination and iatrogenic vaccination to occur before they get there, otherwise it’s not going to be very effective and, and in the case of your kids, they frequently bring those respiratory pathogens home to you,” Ellis says.

Parainfluenza-3 virus

PI3V is included in many viral respiratory vaccinations, but as a disease itself it is significant? PI3V is not usually implicated in mortality by itself. Even in experimental situations, there is generally not going to be deaths without secondary bacterial infection. Ellis says in cow colostrum samples it’s virtually impossible to find a colostrum sample that doesn’t have antibodies to PI3V, which implies that it’s endemic at some level, and is widely vaccinated for. “It’s all over the place. Similarly to the situation in human medicine where they focus on RSV, it’s certainly still a major league player. There are not a lot of data that substantiate that, at least recent data from the United States. I’d be very surprised if it didn’t play a role in BRD, and I guess probably the best way to prove that is to just stop vaccinating for it.”

One of the problems with quantifying the significance of PI3V, says Booker, is lack of updated research. “There has been a lot of research done on BRSV, BVDV and BHV-1, some that is older, some that is newer, but if you go try to look for research on PI3V, there just isn’t much of it there.”

Ellis says there is a lot of good research on PI3V, but it’s old. One of the factors contributing to a failure to implicate PI3V is that it’s difficult to isolate because it’s shed for a relatively short time and it is labile. “You have sample at the right time, optimally four to five days after exposure,” he says. “You’re very unlikely to find it, or virtually any other respiratory virus, if you look with immunohistochemistry in the lungs of dead animals; it’s just gone. The viruses are there and gone, and you’re not usually going to find them postmortem in feedlot cattle that are sick for more than a week. So I think from a diagnostic perspective we have a sampling bias that has led to the false negatives in terms of its involvement.”

Booker says if you look at the seroepidemiologic work, there’s not really good evidence, at least in Canada, that evidence of PI3V antibodies prior to feedlot arrival are associated with the subsequent occurrence of disease. “That’s different than the other three viral pathogens,” he says.

IBR at the feedlot

When Booker went to veterinary school, the most common pathogenesis of feedlot respiratory disease a.k.a. shipping fever, was infection with a respiratory virus — either a virus associated with a respiratory disease or an actual respiratory virus — and it was most commonly thought to be from bovine herpesvirus-1 (BHV-1), which causes infectious bovine rhinotracheitis (IBR). “Having immersed myself in the field side of things, I’ve found it does occur, I’m just not sure it occurs that commonly, now or even 25 years ago,” Booker says.

Ellis says Booker is referring to Martin’s work from eastern Canada which found very little IBR when they actually looked for it. “In western Canada we found very little association between BHV-1 titers and protection or susceptibility to disease,” Booker adds. “If there is one common virus that everybody vaccinated for, it was BHV-1, even at the cow herd level, so that may be a confounding factor.”

How BHV-1 works

Bovine herpesvirus-1 enters epithelial cells (and eventually nerves) in the upper airways of the respiratory system. Erosions and ulcers in the upper respiratory tract, notably the trachea, are the pathological hallmark of BHV-1 infections. These lesions occur from the lysis of infected cells which involves cell death by both necrosis and apoptosis, or programmed cell death. Widespread lysis of ciliated epithelium in the trachea disrupts the housekeeping functions of the mucociliary escalator, and results in a failure to clear bacteria from the upper
airways, thereby resulting in deposition of bacteria in alveoli.

One way the virus can be shed and spread is when the latent BHV-1 in a carrier animal recrudesces in situations such as stress. “There’s certainly the potential for that latency,” says Givens. “We’ve also seen that effective subcutaneous vaccination against BHV-1 does not prevent infection of the exposed animal and resulting nasal shed of low concentrations of BHV-1,” he says. “In contrast, calves that are vaccinated well for BVDV will not have a nasal shed of BVDV after they are challenged or exposed, but that’s not at all the case for BHV-1. Well-vaccinated calves for this herpes virus will shed a significantly lower titer of virus, but 70% of subcutaneously vaccinated calves that are challenged with BHV-1 by natural exposure to acutely infected animals will have some nasal shed of virus.”

It’s a little bit of a different game, Givens says. “You’ve got those latently infected animals that when stressed certainly can recrudesce and shed some virus, but it’s interesting that calves that are effectively vaccinated and protected from disease, meaning you don’t see the spike in temperature or other clinical signs, still are likely to shed a low titer of BHV-1 from their nose. We realize that BHV-1 is replicating in those peripheral epithelial cells and being shed into the environment before the immune system totally gets to it.”

Ellis says that’s true for PI3V and BRSV in terms of shedding and he believes part of that is due to the fact that we get clinical efficacy with parenteral vaccination to reduce shed, but to prevent infection, at least in the short term, we need an IgA response. “Parenteral vaccination usually doesn’t give a very robust IgA response,” he says. “Most of the efficacy studies done today have been done with parenteral vaccination and I think one of the big confounding variables is maternal antibodies at the time of parenteral vaccination.”


Herpes viruses in general have a relatively short duration of clinical immunity; it could be over by 3 months of age, and they generally don’t elicit a very good antibody response to begin with. “I think we tend to disregard the importance of antibodies in reducing infection,” Ellis says. “T-cells are really only efficacious once a cell has been infected. So if you want to reduce the chances of shed and spread in an outbreak, what you really want is a good antibody response, and herpes virus antibodies tend not to be very high to begin with; following vaccination they tend to fall off rapidly. So that’s probably why re-vaccination, or re-exposure is necessary to boost that immunity and reduce infection.”

Lechtenberg says it’s a common practice to boost with a modified-live IBR vaccine when cattle are re-implanted. “The major cost associated with re-vaccination when were facing an outbreak is all about the logistics of putting the cattle through the chute and the negative performance affect associated with the chute trip,” he says. “It has little to do with the cost of the product administered. I think it’s the BRD cases that can happen with certain groups of cattle on feed for 90–100 days are the reason that many sets of cattle have the IBR boosted. 

Booker doesn’t think there is very good published data that shows that routine revaccination of cattle with IBR vaccine at 70, 80, 90 days or whenever they come back through for re-implant, prevents late-days-on-feed respiratory disease or more specifically, IBR outbreaks. ”But having said that, probably any of us who have been in private practice have been through feedlots that have had IBR outbreaks and have found classic cases of clinical IBR. It’s a pretty nasty disease syndrome when it goes through a feedlot, or any group of cattle for that matter.”

Booker says he goes back and looks, there’s usually been some break down in the revaccination programs so that there are extended periods of time when large groups of animals in a feedlot haven’t been routinely revaccinated. “And in feedlots with a very systematic management style where things don’t get missed, you hardly ever see an IBR case pop up. We had a feedlot where we had a full blown IBR outbreak in western Canada this January–February–March, but we haven’t seen one for a few years.”

BHV-1 diagnostics

Clinical examination, post-mortem examination and nasal swabs for laboratory confirmation of clinical cases are common ways to diagnose IBR. Booker has had both viral cultures and polymerase chain reaction tests (PCR) done at two different diagnostic laboratories.

Ellis says it’s not hard to isolate BHV-1. “If you’ve got to be dealing with one respiratory virus in terms of diagnostic approach, BHV-1 is probably the easiest to deal with because it’s pretty straightforward to culture,” he says. “There is a lot of it generally shed, and it’s pretty robust compared to the other respiratory viruses. The paramyxo viruses in general are a lot more difficult to culture Coronavirus requires a special cell line to culture; BRSV and PI3V are labile. BHV-1 is pretty straight-forward.” 



Acute interstitial pneumonia (AIP) can be confused with BRSV, but they are very different. “From a clinical perspective in the live animal they look the same because affected animals have trouble breathing, trouble moving air out of the lung, so clinically they look very similar,” Calvin Booker, DVM, explains. “Once they’re dead though, AIP and BRSV look like different lesions on postmortem and the clinical progression or picture is different.”

Booker says the type 2 pneumocyte hyperplasia in the chronic stages of the process in the lung looks the same. But AIP usually happens in heavy cattle, long days on feed and closer to slaughter weight. “We don’t usually see BRSV in those populations probably because they’ve been exposed to the virus much earlier in their stay in the feedlot with the exception of some really bizarre circumstances when the cattle didn’t get exposed or vaccinated,” he says.