How does BLV cause disease?
When an infected cell with an integrated BLV virus (provirus) is transmitted into a new host, the BLV provirus is expressed into viral particles that infect other B lymphocytes. Active BLV replication reportedly causes a “flu-like” syndrome, as is seen during primary infection by HIV in humans. Within a few weeks, the host’s developing immunity shuts down transmission via viral particles, and the provirus-carrying cells thereafter proliferate only by clonal expansion (infected cells dividing to generate more infected cells). This phase extends for several months or years and is characterized by immune dysfunction. About 60-70% of BLV-infected animals remain in this aleukemic stage as asymptomatic BLV carriers. These aleukemic animals can only be identified by their BLV antibodies and/or of presence of BLV DNA12.
After a latent period of months to several years, at least 30-40% of BLV-infected cattle develop a polyclonal expansion of B cells carrying the BLV virus within their genome, resulting in a dramatic increase in the number of circulating lymphocytes (above 10,000/mm3) 9,12,13. This phase is referred to as persistent lymphocytosis and is associated with immune disruption and inadequate defense against pathogens and opportunistic infections. Animals with persistent lymphocytosis may not show any apparent clinical signs. However, it has been shown that these animals have depressed immune systems. This phase is usually stable for several years, but can progress to tumor development.
Tumors develop when a single infected cell (monoclonal) – or in some cases a few cells (oligoclonal) – undergoes genetic mutation and multiplies to form a solid mass12. Lymphoid tumors that develop in lymph nodes or other organs are called lymphoma9,12. Tumors occur in up to 5% of infected animals, mostly in older cattle that have potentially been infected with BLV for a long time9,12. About two-thirds of the animals who develop tumors previously had persistent lymphocytosis, however lymphocytosis is not a prerequisite for tumor development and tumors can occur in aleukemic cattle9,12.
The tumor phase is characterized by progressive loss of body condition and generalized weakness12. The specific clinical signs will depend on which organs are affected. Common locations for tumor development include the lymph nodes, the heart, the abomasum, the uterus, the spleen, the caudal spine, the liver, the kidneys, and in the space behind the eye. Heart symptoms can resemble chronic heart disease with increased heart rate, difficulty breathing, jugular pulses, abnormal heart rhythm and sounds, or heart failure. Tumors in the abomasum can cause pain, loss of appetite, diarrhea and/or constipation. Splenic tumors can rupture leading to sudden death from internal bleeding. Extradural spinal tumors can compress the cord or spinal nerves causing hind limb weakness or paralysis. Tumors in the uterus can result in reproductive failure. Tumors in the space behind the eye can cause the eye to bulge out and become irritated. Once animals progress to the tumor phase the disease is ultimately fatal12.