The Biology of the Caprine Arthritis Encephalitis Virus

The CAE Virus and the Immune system

Envelope Protein The surface and transmembrane portions of the CAE envelope protein antigen is shown here as simple, smooth shapes. In reality antigens are large proteins composed of strings of amino acids that are folded tightly into specific, complex conformations.

Protein For instance the image on the right shows an imaginary protein. It consists of a long string of 64 amino acids each represented by a green ball.

The envelope protein of the CAE virus has over 900 amino acids which are folded into an extremely complex shape.

The immune system can make many different antibodies to various regions within the antigen protein. These regions are called epitopes. Researchers have so far identified at least 11 different antibody binding epitopes on the envelope protein of the CAE virus. In the image below, the envelope protein of the CAE virus is shown untangled and stretched out with the approximate antibody binding regions. At this time six different antibodies have been identified that bind to regions of the transmembrane portion of the env protein (called TM1 through TM6), and 5 different antibodies that bind to the surface component (called SU1 through SU5).

Regions of antibody binding

Seroconversion

When the goat is first infected with CAE virus the immune system will slowly begin to produce antibodies to various regions of the envelope protein and to the capsid protein. Called seroconversion, this process may take only a few weeks or as long as several months. Goats develop a strong and early antibody response to the surface epitopes SU3 and SU5 with the levels remaining constant over a long time. Antibody production toward the capsid protein gag also occurs early but the level of anti-gag antibody decreases slowly over time. Goats develop antibodies toward the transmembrane portion of the envelope protein much later in the course of infection but an early strong response to several transmembrane (TM) epitopes can predict the appearance of severe symptoms.

Antibodies to different antigens of the CAE virus can rise or fall (sometimes to undetectable levels) over the course of time. It isn't certain why this happens. It could be due to the high variability of field strains of the virus or to the genetic make up of individual goats. Antigens developed from experimental strains of the virus may be different from antigen of the more variable field strains. In addition, antibodies can disappear in the case of severe clinical symptoms, yet animals with no symptoms have detectable antibody levels.

Symptoms of CAE and antibody production

There is a strong correlation between the development of severe arthritis and high levels of the TM3 and TM4 antibodies, especially TM3. It is not very well understood why high levels of TM3 antibodies cause the severe symptoms of CAE but it is suggested that the antibodies somehow play an important role in the disease process possibly enhancing the infectivity of the virus. It has been shown in other animal models that vaccination with similar retroviral antigens result in a high viral load with more severe symptoms rather than preventing viral infection. Vaccination attempts in goats have not been promising in that the vaccines do not control or prevent virus replication and may even enhance or cause severe symptoms of arthritis.

CAEV antibodies and immunity

Goats that have been infected with the CAE virus for a long time but do not have symptoms have lower anti-CAEV antibody titers. Antibodies against the CAE virus are not able to neutralize the virus for reasons that are not understood. Instead, the presence of CAE virus is very persistant in spite of the fact that the immune system mounts a strong immune response. Even in a small minority of goats that are able to produce antibodies that seem capable of neutralizing the CAE virus, these neutralizing antibodies are produced very slowly and in very small amounts and free CAE virus can be found in synovial fluid and blood.

Next:Testing for the CAE virus with ELISA