super excited to be here and um as you have questions I find it's easier to just plop them in the the Q&A box right away and then hopefully we can address them um throughout the webinar today I was tasked with giving you the dis the basics and overview of bovine leukemia virus today Um and then I'll be joined Phil will will talk about some of the um consultations and and ways we use the data that I will hope hopefully set up foundational knowledge for his presentation Um let's see I have it on this slide and I depending on um what
    
    your view looks like there should be a black box with a smiley face There will be no content um or anything important in that black box So if you need to move part of your um video imagery or the control panel if you put it up here in this upper right hand corner you're not going to block anything on the slides So I'll give you a minute to get adjusted And I'll tell you what I'm going to do the same Hopefully I'm a little bit still a little rusty with with Zoom It's been a little bit since I used it but okay So today my
    
    thought was to cover the five W's and the one H the the who who gets BLV what is it where is it coming from when why and how do we manage it in any corner where you see the Spartan helmet from Michigan State University that's going to indicate work that someone um whether it be my team or teams before me or at the same time but it's work that's done through Michigan State university and I did use a lot of QR codes or I have some QR codes So if you want to link to the references you might have your cell
    
    phone handy or a way to get those QR codes And of course I'm happy to share share them with anyone to distribute later So let's just jump right into it What is boine leukemia virus It's a delta retrovirus And what a retrovirus does is it integrates when it infects an animal it integrates itself into the host genomic DNA So the virus itself is an RNA virus goes into the cellular mechanisms of the cow or the animal that it's infecting and it integrates itself into um the cow's DNA or the cow's genome It likes to target B cells Um and
    
    when it does that so so B cells are um a cell within the blood So this is a bloodto blood a bloodborne um virus or bloodto blood transferred virus When the viral DNA integrates into the host DNA then it is called a provirus So you'll hear me talk about proviral loads a little bit later in this presentation That's what I'm talking about It's it's the virus when it's integrated into the cow or the host genome So it targets B cells The virus targets B cells B cells are responsible for the adaptive immune
    
    system of an animal and that they produce antibodies to fight um pathogens or infections What happens when a B cell is infected with bovine leukemia virus or BLV The signals are not received there those B cells are not as functional as a healthy B cell So the signals are not received by B cells There's improper maturation of the B cells that are infected with BLV There's decreased antibbody production and really a compromised immune memory and a compromised immune system which MSU Dr Cousins had done some work um a few
    
    years ago and and I'll show you some of those graphs from his research Bovine leukemia virus is the virus and you might hear boine lucosis Bovine lucosis is what the animal um succumbs to or or is the disease if you want to think of it that way When do cows get it Um there's vertical and horizontal I'll just throw it all up here Vertical and horizontal transmission So think anything that's bloodto blood transfer This virus is in the cells in the blood So we can have placental transmission The virus is
    
    small enough to go through the the placenta So from dam to calf There's blood to blood or blood exchange at birth And they have colostrum and milk on vertical and horizontal transmission in that um depending on your research area or who you talk to they can be considered vertical or horizontal um vertical if it's the dam and the calf that are the parental pair But sometimes on farms we have mixed colostrum or the colostrum and milk is not coming from the dam herself It's coming from somewhere else on the farm Um that then
    
    would be horizontal transmission So the virus is in that colostrum or milk It can pass then into the offspring If it's frozen um or pasteurized colostrum it's processed the virus is not um alive or it's not able to infect the calf at that point Horizontal transmission is then between herd mates and any again think anything bloodto blood transfer So biting flies they've they found BLV in in biting flies The use of needles um and sleeves natural breeding dehorning and tattooing and foot trims are all areas
    
    more common areas that and research that we found there's bloodtoled blood transfer So there's bovine leukemia virus transmission My slides won't advance This is good Um there we go So who gets infected Um this is a group of of dairy producers or dairy interests So there it's it's infected in young stock and adult animals of dairy animals Beef animals are not excluded Neither are bison buffalo yaks camels and um sheep and goats have also um get infected with BLV sheep and I believe goats also once
    
    they're infected with bovine and leukemia virus succumb to the virus fairly quickly where cattle it can render um it it stays hidden from the immune system and it doesn't lead not every single animal subsumes to boine leukemia virus not every single animal gets the tumors but in sheep it's a different story I just wanted to put that out there but I know this group is dairy focused so we'll stick with the dairy animals for today So why should you care And this is where I'll spend most of my time today um and where I bring the
    
    research and what our our group or or people individuals of the MSU extension and research team have found So um there was a study that looked at a little 3,611 dairy cows from 91 different herds across nine states I think Phil references part of this study too in his slides coming up They found positive cows so cows that were infected with the virus were 30% more likely to be cold during this 29-month monitoring period as compared to BLV negative animals And so just to set up the future slides like
    
    I did in the beginning the QR code down in the bottom right hand corner if you scan that it'll take you to the reference So this is a published article peer-reviewed article from um Dr Bartlett did this work and the Michigan State helmet because it's Michigan State work The other thing I mentioned was that animals with BLV infections they have a compromised immune system So this was a Dr cousin study and what they did was they they took BB positive and negative animals and gave them a vaccine and then looked at titers or antibbody
    
    responses to those vaccines The dark bar the these are just figures from that paper Again if you want to read the paper look at the figures and the descriptions that QR codes in the bottom right hand corner So the black bars on this graph are um the percentage of cell types found in BLV negative animals of that study and the light gray are the BLV positive animals So CD4 CD8 or the the the the cells represented in the red box here you can see they are they're TE-C cells So um TE-C cells are involved with
    
    directly killing cells infected with a virus or recruiting other immune cells when encountering a pathogen And you see that all three of those cell types are lower had a lower percentage in BLV positive animals So they're not having this they don't have the higher percentage or as as many cells that are involved with killing other cells infected with virus that compromised immune system These bars here are of B cells and we see that the BLV positive animals had a higher percentage of B cells in
    
    the study But that's not a surprise one it's the first line of defense when encountering a pathogen And these animals were selected We knew they were BLV positive which is a a virus So that the animals already mounting an immune system and trying to fight off the virus So we're not surprised that they have a higher percent of B cells But when we look at the response of antibodies to they they um the vaccine they used was the Bova Shield Gold So these are all um incorporated into that vaccine So these
    
    are the ano what you're looking at on the lines are is the antibbody response the OD um from the vaccine So BLV negative animals are these I don't know if you can see my mouse but BLV negative animals are the solid black line and BLV positive animals are that light gray dotted line and across all three of the components that were in the bova shield vaccine you see a lower antibbody response in BLV positive animals so they're not able to mount animals with BLV infected with BLV aren't able to mount that immune response and be
    
    protected from the vaccines like a BLV positive animal would That's not all Um so we also found um Dr Norby and Erskin Bartlett this was an a Michigan state study as well found that the animals with increased levels of bovine leukemia virus have decreased milk production Um the study out of Canada found that animals with BLB higher levels lots of virus circulating in the animals system they had lower milk components And just to not make it all MSU study focused we our research is also supported by others or others support
    
    what we're finding as well Um that animals with BLV are likely to be called earlier They have lower production if they're infected in the first and second lactation That's a study out of Canada And then um while it's a study in buffaloos uh they found decreased reproductive performance and lower mount production in um buffaloos in in Egypt We to date all the research that's looked at reproductive success in animals in BLV I haven't seen anything with um dairy cattle but I I wanted to be complete in what I've shared with the
    
    literature This isn't it This is just a snapshot of some of the research that's out there Recently we had a master student graduate and I say recently it's probably been two years now that they did a partial profit loss with some of the farms we've worked with and they estimated the BLV impacts on a per cow basis which because BLV affects the the welfare of the animal and their immune compromise they're more likely to be sick with other illnesses So sometimes it's hard to toss out especially when you're
    
    looking at budget piece out what's due to BLV what's due to some other things because it's all it's integrated within that one animal So we tried to in this study Um and we looked at things such as vet labor costs drug costs um breeding costs and things like that that were on the farm Um and we estimate an average partial profit loss of a BLV positive cow to be somewhere between 2004 $400 per lactations So hopefully I'm I'm showing you evidence of why you should care I have one last thing to bring up Um and
    
    that's the condemnation So when an animal submitted for slaughter 22 and a half and this was an estimate or records from 2009 So um I apologize that's the most recent one I have Um but 22% of the cow condemnations coming through the the slaughter plant or the harvest location were condemned due to lymphoma And of that the dairy cow condemnations of the combinations of dairy cows was 26 or almost 27% due to lymphoma you know what I'm um and how can it be combed So one thing it's all right I'll get there I I think
    
    my slides are missing some slides but that's okay If they're not in there I'll I'll go back and cover some bases So boine leukemia virus has there's two ways to test for it or or diagnose Um one is Eliza and the other is through qPCR or PCR Eliza historically has been the test that's been used It detects antibodies to BLV So it's a serial conversion in an animal And there's multiple samples that you could use and run Eliza on or submit for the lab to to run ELISA And that's milk serum or plasma are the most common What
    
    an ELISA does is it detects the presence of um antibodies or that serero conversion So while it says the animal was infected at some point with BLV it's not um indicative of a current BLV infection or a new infection Um it it's low cost The results come back fairly quickly Um but it is unable to discriminate between maternal passive antibodies and active immune response So if you talk to anyone that's running the Eliza's or the labs they'll suggest that you wait for the animal to be old enough that they have an active immune system
    
    and they're not protected by those maternal antibodies because the Eliza wouldn't doesn't discriminate between the two The qPCR and I and I don't want to steal some of Phil's thunder that you'll hear from him later I'll just set up what it does and what it's telling you So PCR is they're actually amplifying that provirus So the provirus again is bovine leukemia virus that has integrated into the host DNA into a B cell It's DNA it's viral DNA That PCR detects the DNA of the virus Typically we use blood a blood
    
    sample to run that assay Um there are you could use other biological samples but since the virus lives in B cells which is a blood cell a blood sample is is the best sample to use when running PCR It's BLV specific It's able to be performed on multiple sample types like I said So anything that you can extract DNA from um it has undetectable levels are possible So you could you get a quantitative um result So how essentially how much provirus is in that animal or how much virus is the animal harboring The downside is you wait a
    
    little bit longer for results It's a longer assay to run and it may be cost prohibitive So we run samples or we've worked collaborated with central star and elizas are on the range of4 to $6 and qpcr is more like $10 to $15 There's an example like I said we we've worked with central star and this is just example of the output that they provide Um this is what you would get as a producer or veterinarian after you submit samples Your Eliza results come back as positive negative or suspect So in that final results column all the way
    
    on the right you see they're all Ns or negatives The test value is the optical density of the ELISA And really we haven't found anything um with related to or associated with proviral load at an OD value So I just wanted to let you know that's what it was but it doesn't correspond to amounts of virus or anything like that in these eliza tests or assays where qPCR or qPCR um gives you that proviral load So that the sequence or amount of virus you have an undetected low moderate or high So central star categorizes how much virus
    
    is in those animals into those categories and that's what they give you as these final results So down here in this bottom table in final results you see one animal was undetected and one was low So low amounts of virus The test value is that proviral load So um the way they this is a ratio of animal cow DNA to viral DNA So the larger the number the more virus you have in that animal And you see zero is undetected They were unable to detect or have a threshold of virus in that animal And then low is this
    
    0.06 High would be above one Okay So one thing that we've done um when we talk about how this can be combed with bovine leukemia virus and I Phil will go into a little bit more detail on these so I don't again don't want to steal his summer thunder but I'll I'll set up a little bit about what our team has done We lead consultation discussions and do herd scans So part of the consultation discussions include the BLB cow list so you can you you know or can rank animals on how much virus they have We look at the herd BLB
    
    prevalence to have those discussions tracking over time You identify new infections and maybe where those infections are coming from We look at prevalence by lactation and shedding by lactation Shedding Um when I say shedding I'm referring to the amount of virus in an animal that's that's infecting herd mates or potentially infecting their herd mates Distribution of shedters So again shedddters are those animals with higher levels of virus that are more likely to infect their herd mates versus animals with
    
    lower amounts of virus And then we go through management notes So what are things that we could do or that the farm could do the veterinarian can do that will combat some of the bovine leukemia virus infections that are happening on the farm Things we talk about Again I don't I I put Phil's picture here to remind me that Phil's Phil's going to um hit on some of these things but things to consider or things that we talk about are day-to-day management things So the testing how are what are you doing with
    
    needles and sleeves Um and you know if you're unable to use a single-use needle maybe there's other management strategies that we can discuss that would help or um not do the blood blood transfer from positive to negative animals to cause more infections Maybe it's a third strike So we know that when you're selecting or when farmers are selecting for individuals to keep on the farm or retain and get rid of um there's a host of traits that they're looking at maybe BLV infection could be one of those strikes against the animal and
    
    proper hygiene on the farm We also talk about big picture management So testing and calling animals monitoring animals segregating them placing positive ones on a do not breed list or breeding to beef Um reducing the number of purchased cows and then testing those purchased cows There's and I'm sure in discussion and if you have other ideas or questions I'm sure there's other management strategies that um that could help These are these are the ones that we go to when we start those conversations with
    
    with producers One thing and this is um I like to say hot off the press This is Madison my PhD student and she's been working on the last 5 years we've been following calves on the farm and sampling them to see where um in the life of a young stock animal infections are coming from Um and I'm here to tell you that every farm is a different story BLB solution and management is not a one solution fits all And that's why these consultation meetings and conversations are so important So we we followed five
    
    farms for the last five years and each farm has a different story about um where those infections might be coming from or how what's the best management strategy for that farm One thing that we did find with her data set though was that calves born to a bov positive dam were three times more likely to be bov infected within their first year of life And this was something this project all started from the consultation meetings we had with farmers They were they noticed that and they noticed that
    
    they had positive dams The calf was more likely to be positive So we just put the research behind it Um we also found that daughters of dams from a higher proviral load so animals that had higher viral levels their daughters had a greater likelihood of testing positive for a higher um proviral load category in their life as well So damps that had high proviral load their daughters were more likely to have high proviral load in their life as well So um daughters born from Eliza positive or high proviral load dams have an
    
    increased risk of being affected by the virus as well You might ask why Um granted that will be the next study but we do know there is literature out there and some that our group has done that there are genetic markers for resistance and susceptibility to BOV whether we didn't sequence these animals So I I can't comment on that with this particular study but there are other studies We know that there's genetic markers um that are resistant to bovine leukemia virus So while the animal can become infected they never get up into
    
    the higher categories of PVL Um they never reach the high levels Um they stay the lower levels stay maintained in that animal through its lifetime The one thing and I'm I'm kicking myself because I don't know where my slides are Before I before I close I there were a series of slides about um BLV progression and how the de disease progresses So when an animal becomes infected with BLV um one a few let's say a few B cells become infected and that virus may lay latent meaning that those cells don't
    
    don't um divide um the virus stays in low levels and it that animal can stay in low levels of that provirus um that virus laying latent for its entire life and we never have any issue Um there are animals that once they become infected those the B cells get infected Those B cells start to divide The virus also infects other B cells and all of a sudden that animal escalates to a high proviral load category And when that animal has a high proviral load if they survive they maintain or keep that high proviral load We don't see a lot of
    
    animals that bounce back and forth um from high high viral loads to low and then to high again or or medium and moderate Um we see animals that that they maintain whatever that level is until they don't and there's some switch and we still don't know what that switch is um there's some switch that triggers it and the animal maybe has low low amounts of virus for up to the third lactation and then the fourth lactation something and the the switch happens which welcome to research we need to figure that out
    
    Um but the switch happens and the animal could could succumb to the virus um become high proviral load typ typically growing tumors at that point and and getting lymphosaroma and I apologize I have I had slides with diagrams of that and I don't know where it went in my slide deck um but it it's one thing to think about of of how that virus progresses and um animals with low prival proviral loads just may stay low until one day they they don't and then at that point it's it's too late to save the animal That's that's really all I I
    
    had I'm I'm open to discussion I hear what questions you have or or something that was unclear that I could clear up for you Are there any questions from anyone out there Uh I did uh we don't have any questions in the Q&A yet at the moment but I had a couple of questions So you just touched on in that slide previous to this one about essentially genetically uh susceptible or genetically resistant cows to this disease Are there any other kind of genetic markers that have u come about any kind of like health traits that may
    
    increase or improve a cow's likelihood of surviving this or fending it off That's a that's a great question So the genetics work to date has really just focused on a a particular region and a particular gene Um and that gene is uh the the one that how do I want to it's it's bola or MHC region and so it's responsible for the antibodies and creating an immune response It's it's the h one of the health genes that they use in um the holene prediction and the indexing research to date has not looked
    
    for to answer your question No there's no research that has looked for other genes or other health traits that are associated with this that that might help Um but it's a it's a great question and and if we ever get research dollars back um it's something that would would make a really nice project All all the projects have date have really just focused on one gene one region in that in that va gene Okay I had another question about uh what kind of I don't want to take away Phil's thunder if he's got this in his
    
    presentation but we'll give him a challenge It'll be okay What kind of prevalence do you see in herds in general And does prevalence vary depending on herd size Yes So I let me try to go if I have a little bit of time Let me because my slides went advance earlier I wonder if I went I did There they are So here if if I can take a a few minutes So this is the disease progression diagram Um I did have this slide So you see um we have a few of the cells that become infected The animal becomes alukemic Low small
    
    amount of virus 30 to 40% of those animals then move into persistent lymphocytosis So there's more cells that are infected and then very few go to tumors and at that that point that that animal is unwell or deceased Where is it and on the herd This kind of gets to your question and if I don't completely answer it make sure to to ask again But 94% of the dairy herds have at least one animal infected with BLV The average herd prevalence is about 46% We like to say 50% Um and it it depends from farm to farm
    
    I've seen very large farms that have a low prevalence I've seen small farms that have a high prevalence Um and and Phil it's okay if you wanted to unmute and comment on some of the things that you've seen as well Yes I indeed I've seen high prevalence in in herds have seen up to 90% prevalence in a herd and it doesn't seem that farm size is the issue However I'm going to mention some negative herds and uh it may be that negative herds typically tend to be smaller because they haven't purchased animals So
    
    because it can be purchased in um if the the few percent that are negative typically tend to be smaller but once a herd is infected then size is not an issue Okay You have any other slides you'd like to still share No I'm so sorry I they couldn't they wouldn't advance and then I guess it Welcome to computer and technology problems So let me get to the end and then Oh goodness Yes I do have two more slides I would like to share So uh we have and apparently they're on automatic Oh my goodness So we have a a virtual
    
    conference this year focused on BLV July 16th and it'll be it I put it in your time zone So it's from 10 to noon We'll have flash research talks So very quick snippets of what the research team is working on And this is not just just us This is international So you'll hear the folks from Canada um Argentina all Japan Um they're all working on BLV and we all come together once a year So we'll have some some flash talks from 10 to noon on July 16th On the 17th producer focused discussion So if you'd like to come to
    
    the table and ask questions um share concerns listen to others the ones that we consult with hopefully will join have have an open forum for discussion for the producers veterinarians anyone that's on the ground working with BLV and the animals or wants to learn more And then the 18th is focused on building research collaborations and writing those next projects So QR code is for registration and more information in the bottom left hand side of your screen And if you're um would like to join the BLV list serve there's an email
    
    list serve you can scan this QR code And if you don't want anything to do with QR codes feel free to send me an email My email is down here in the bottom right hand corner and I'm happy to share any of the resources connect you or answer any questions that come up that maybe don't come up today but tomorrow when you're stewing about VLB.