Infection and Clinical Signs
Bovine Herpesvirus-1

Epidemiology

BHV-1 has a restricted host range (i.e. bovids) and seldom crosses the species barrier (Brake & Studdert 1985). BHV-1.1 infections are most common in feedlot cattle (Merck, 2005).  Infection is usually for life and carriers are asymptomatic unless the virus is reactivated (i.e. by stress). The duration of shedding is approximately 10-14 days during acute respiratory infection (Gibbs & Rweyemamu 1977) and also occurs following stress-induced reactivation of latent virus. Horizontal transmission can occur via contact with infected nasal droplets or contaminated semen (Mars et al., 2000; Kahrs, 2001).  BHV-1 is also vertically transmitted between pregnant dams and their fetuses (Miller et al., 1991).

BHV-1 is not abundant in the environment. It is very susceptible to changes in temperature and humidity (Elazhary and Derbyshire 1979; Mars et al. 1999) and easily eliminated by common disinfectants and solvents (Gibbs, and Rweyemamum, 1997). Although, infection can occur via inhalation of aerosolized virus, this is not likely a major cause of infection.  Aerosolized virus does not appear to be able to travel greater than two cow-lengths (Wetlink et al., 1993). 

Although Whetstone and Evermann (1988), reported that BHV-1 infection caused clinical disease in sheep and goats, this may have been specific to a certain strain of virus. As a general rule, clinical BHV-1 disease does not occur in sheep under natural or experimental conditions (personal communication with Dr. Philip Griebel; Young, 1993), despite the presence of BHV-1 cross-reactive antibodies in most sheep (personal observation).

BHV-1 is not zoonotic and at this time, Denmark, Sweden, Finland, Switzerland, Austria and the Italian province of Blozano have successfully eradicated BHV-1 from their bovid herds. Germany implemented a BHV-1 eradication program in 2004.


Pathogenesis

BHV-1 entry occurs at mucosal surfaces.  BHV-1 receptors are expressed on the surface of epithelial cells of the upper respiratory tract, vaginal or prepuce mucous membranes, and the tonsils and conjunctivae (Tikoo et al. 1995a), as well as CD4+ T cells (Lovato et al. 2003), monocytes and macrophages (Nyaga & McKercher 1979; Forman et al. 1982). 


Entry of the virus into the cell involves the interaction of a number of glycoproteins, including glycoprotein B (gB), glycoprotein C (gC) and glycoprotein D (gD) (Li et al., 1995). BHV-1.1 gC and BHV-1.2 gC differ from one another (Rijsewwijk etal., 1999) and may play a role in fetal infectivity. gC and gB are involved in the initial binding of heparan sulphate on the cell surface. This is followed by binding of a high affinity viral receptor, fusion of the viral envelope to the cell membrane and release of the virus particle into the cytosol where it is transported along microtubules to the nucleus for replication using host proteins. Viral replication occurs within 2 hours of the animal becoming infected (Meurens et al., 2004b) and viral release and spread is detectable within 8 hours of infection (Babiuk et al., 1996).  

Cell-mediated immune pathology occurs approximately 7 days post-infection (Engels and Ackermann, 1996). Infected cells can also undergo virus-induced apoptosis (Lovato et al., 2003). Denuding of the respiratory mucosal epithelium by apoptosis or immune activity, results in increased susceptibility to secondary bacterial infections which can result in pneumonia and even death (Hanon et al., 1998; Lovato et al., 2003). 

BHV-1 also has immunosuppressive properties. Infection of monocytes and macrophages interferes with antigen-processing and presentation as well impairing phagocytosis (Nyaga & McKercher 1979; Forman et al. 1982). BHV-1 also expresses a protein that binds complement factor C3, thus inhibiting the complement cascade (Huemer et al., 1993). With respect to neutrophils, there is a decrease in the circulating number in blood and their activity is diminished (Tikoo et al., 1995; Forman et al., 1982). Infection of CD4+ T cells results in lower numbers of cells in the circulating lymphocyte pool, decreased IL-2 expression and decreased cytokine secretion following stimulation with mitogen (Forman et al., 1982; Winkler et al., 1999). BHV-1 gG has the ability to bind and inactivate a number of chemokines, thus contributing to suppression of the host immune response (Bryant et al., 2003). 

Regardless of whether the initial infection is symptomatic or asymptomatic, infection always results in latency. Latency is another method of evading the immune response and most often occurs in peripheral nervous tissue, specifically the sciatic and trigeminal nerves, which is immune-privileged and do not express class I MHC molecules (Rock et al., 1992; Rock, 1994). Latency may also occur in tonsillar-resident lymphocytes and peripheral blood lymphocytes (Mweene et al., 1996). Cattle with latent BHV-1 infection may be seronegative for BHV-1-specific antibodies (Hage et al., 1998). Re-activation of latent virus by stress, such as shipping, results in shedding within 1 to 4 days and may also result in the appearance of clinical symptoms within 1 week of the stress event (Thiry et al., 1987).


    Arrows point to infected neurons with BHV-1
                            http://ard.unl.edu/rn/0300/geneticspx1.htm


Clinical Diseases

The severity of BHV-1 infection in cattle relates to the subtype and strain of virus. Respiratory disease is the most common clinical form of infection in non-breeding cattle, whereas, abortion and genital infections are more common in breeding cattle. BHV-1 can also be characterized as either uncomplicated or complicated. Uncomplicated infections do not result in death in healthy, mature cattle (Kahrs, 2001). Complicated infections occur when there is secondary bacterial infection or systemic spread of virus resulting in viremia, and can result in death (Engels and Ackermann, 1996). Fatal viremia also occurs in newborn calves with failed passive transfer of maternal antibodies (Mechor et al. 1987).  

 

Unless noted otherwise, description of diseases caused by BHV-1 are taken from Merck (2005).

Infectious Bovine Rhinotracheitis (IBR)

Most common clinical manifestation of BHV-1 infection in feedlot cattle.
Predominant subtype:    BHV-1.1
Incubation period:         2 – 6 days

Clinical disease:

1. Uncomplicated IBR - Viral infection alone; is not life-threatening.  Most lesions are restricted to the upper respiratory tract and trachea. Recovery occurs approximately 4 – 5 days after onset of clinical signs.

2. Complicated IBR - Viral infection is followed by secondary bacterial pneumonia, which may result in death. Mortality may reach 10 %.  “Shipping fever” is a severe pneumonic condition, that occurs when infection with BHV-1, BVD, parainfluenzae-3 virus, or respiratory synctial virus, is followed by secondary bacterial infection with Mannheimia hemolytica and/or Pasteurella multocida (Yates, 1982).


Infected bovids may have mild to severe clinical signs which include: high fever, inappetance, coughing, difficulty breathing, excessive salivation, nasal discharge that progresses from serous to mucopurulent, conjunctivitis with lacrimal discharge, inflamed nares to give th appearance of having a “red nose”, and dyspnea if the larynx becomes occluded with purulent material. Ulcers commonly appear in mouth and nose. Nasal lesions consist of numerous clusters of grayish necrotic foci on the mucous membrane of the septal mucosa, just visible inside the external nares. They may later be accompanied by pseudodiphtheritic yellowish plaques.


                Infectious Bovine Rhinotracheitis from BHV-1
                    http://www.vet.uga.edu/VPP/NSEP/fmd/Eng/IBRdx.htm

Genital infection

Predominant subtype:    BHV-1.2
Transmission:                via mating
Incubation period:         2 – 6 days
Recovery from lesions:  Approximately 2 weeks post-onset

Clinical forms of disease:


1. Infectious pustular vulvovaginitis (IPV) (cows) - Early signs: frequent urination, elevation of the tailhead, a mild vaginal discharge; swollen vulva, small papules, erosion and ulceration of mucosal surface, fever, depression, loss of appetite, painful urination, swollen vulva with pustules and discharge. Pain on sexual contact.
Late signs often include secondary bacterial infections with inflammation of the uterus, transient infertility, and purulent vaginal discharge for several weeks. 

2. Infectious balanoposthitis (bulls) -
Infection of the penis and prepuce.  Clinical signs and lesions are similar to those seen in IPV.

Abortion and Stillbirths


Generally occur 1 to 3 months post-infection (Carter et al. 2006). The incidence of abortion does not correlate with the severity of disease in the dam, but is often preceded by pustular vulvovaginitis in the dam and has also been found to occur concurrently with IBR. Fetuses in the second half of gestation have a higher incidence of abortion, but early embryonic death is also possible. Aborted fetuses may have pale, focal, necrotic lesions in all tissues, which are especially visible in the liver.


                        Aborted bovine fetus, mid-gestation
http://www.fao.org/ag/AGA/AGAH/empres/GEMP/avis/B103-brucellosis/tools/0_imag_07-fetus.html                                               


Generalized infection in calves

BHV-1 infection can be severe in young calves and cause a generalized disease, characterized by enteritis and death. Pyrexia, diarrhea, ocular discharge, incoordination, and eventually convulsions and death may occur in a short period after generalized viral infection. Calves might present with a respiratory component that is characterized by: respiratory distress, petechial to ecchymotic hemorrhages in the mucous membranes of the nasal cavity and the paranasal sinuses and focal areas of necrosis in the nose, pharynx, larynx, and trachea. The sinuses and nasal cavity are often filled with a serous or serofibrinous exudate. As the disease progresses, the pharynx becomes covered with a serofibrinous exudate, and blood-tinged fluid may be found in the trachea. The pharyngeal and pulmonary lymph nodes may be acutely swollen and hemorrhagic. The tracheitis may extend into the bronchi and bronchioles; when this occurs, epithelium is sloughed in the airways. The viral lesions are often masked by secondary bacterial infections. In young animals with generalized BHV-1 infection, erosions and ulcers overlaid with debris may be found in the nose, esophagus, and forestomachs. In addition, white foci may be found in the liver, kidney, spleen, and lymph nodes.

Other clinical signs

Conjunctivitis, mastitis, enteric disease and dermal disease may also occur. Any of these signs may occur in isolation or concurrently with other forms of disease (Kahrs, 2001; Wellenberg, 2002).


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