The major targets for FIV infection are activated CD4+ T-lymphocytes. These cells typically function as T-helper cells which have a central role in immune function, facilitating the development of humoral and cell-mediated immunity. The FIV envelope glycoprotein gp120 binds to a primary receptor on the cell surface, CD134 [Shimojima 2004, Willet 2006]. A conformational change occurs in gp120 that enables a second interaction with the co-receptor, CXCR4, triggering membrane fusion and viral entry. The viral enzyme reverse transcriptase that mediates copying of its RNA genome into a DNA copy (or provirus) is error prone and lacks a proofreading function; thus FIV may mutate rapidly and exist as multiple strains. This genetic diversity results in variants that may evade immune detection and is an important consideration in the development of both molecular diagnostic techniques and vaccines.
Latent infection arises when a cell carries an integrated copy of provirus but does not produce new virus particles unless it becomes activated. Latently infected cells represent a “reservoir†of infection that is not susceptible to neutralising antibodies, posing an obstacle for effective vaccination.
In the first few days following experimental inoculation, FIV grows in dendritic cells, macrophages and CD4+ T lymphocytes, and may be detected in the plasma within two weeks. The level of virus in the plasma and proviral DNA in the blood mononuclear cells increases, reaching a peak 8 to 12 weeks post infection. During this period mild to moderate clinical signs such as anorexia, depression, and pyrexia may be observed. These conditions generally subside rapidly; in contrast signs such as generalised lymphadenopathy, due to increased numbers and size of active germinal centres in the lymph nodes, may persist for weeks or months. The decrease in plasma viral load marks the beginning of the so-called ‘asymptomatic’ phase that can last for many years, or may be lifelong. It is assumed that viral replication is controlled by the immune response during this phase while the infected cat remains relatively free of clinical signs.
The final outcome of FIV infection is variable. During the asymptomatic phase the plasma virus load is stable but there is a progressive decline in CD4+ T lymphocyte numbers which results in a decreased CD4:CD8 T lymphocyte ratio [Torten et al. 1991]. In a proportion of infected cats this leads to a functional immunodeficiency, clinical signs of AIDS and death.