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Feline Immunodeficiency Virus (view source)
Revision as of 12:37, 27 August 2010
, 12:37, 27 August 2010→Transmission and Epidemiology
Cats with oral inflammation are probably more likely to shed virus in saliva than asymptomatic cats [56]. Gingivitis, stomatitis, periodontitis, and odontoclasia are among the most prevalent clinical signs of FIV infection [26,54]. concurrent herpesvirus infection [22] although a specific etiologic agent is not usually identified.
Cats with oral inflammation are probably more likely to shed virus in saliva than asymptomatic cats [56]. Gingivitis, stomatitis, periodontitis, and odontoclasia are among the most prevalent clinical signs of FIV infection [26,54]. concurrent herpesvirus infection [22] although a specific etiologic agent is not usually identified.
Seroepidemiological surverys of the prevalence of FIV in the UK have shown that 13-19% of sick cats may be infected with FIV compared to 2-3% of healthy cats.
Seroepidemiological surverys of the prevalence of FIV in the UK have shown that 13-19% of sick cats may be infected with FIV compared to 2-3% of healthy cats.
In multiple-cat households where FIV-infected cats intermingle with uninfected cats, the incidence of transmission over several years of contact appears to be very low when assessed by seroconversion to positive FIV-antibody status [54,62]. However, the transfer of virus through casual contact may be more frequent than initially reported when infection is defined by the presence of FIV nucleic acids and not by the harboring of infectious virus [14]. In a study reported by Dandekar et al, 20 specific pathogen free cats were co-housed with FIV-infected cats for 2 - 4 years, and 10 cats remained seronegative despite yielding FIV DNA from the blood and bone marrow by PCR and FIV RNA by in situ hybridization of mitogen-stimulated lymphocytes. Blood from these cats, however, was not capable of conferring productive infection, and these cats remained asymptomatic for the one-year duration of the study. This restricted form of FIV infection failed to elicit humoral immunity, a finding that resembled later reports of regressive infection of kittens following vertical transmission [1,43]. O’Neil et al. observed that some kittens infected with FIV from chronically infected mothers displayed a gradual reduction in virus load within cells of peripheral blood, resulting in a loss of antibodies to FIV within the first year of infection [43]. In this regressive form of FIV infection, cats lacking detectable FIV DNA in peripheral blood cells often harbored FIV DNA or low levels of infectious virus in tissues such as lymph nodes, thymus, spleen, bone marrow, and brain. Likewise, Allison et al. reported a progressive loss of detectable FIV DNA and infectious virus in peripheral blood lymphocytes over 14-month interval following maternal transmission of FIV belonging to clade A (FIV-Petaluma) or clade C (FIV-Pgmr) [1]. Preliminary data suggest that kittens with regressive infection remain resistant to infection following mucosal challenge [36].
It is well established that FIV is transmissible across mucosal surfaces, including those of the oronasal cavity, vagina, uterus and rectum [6,10,31,32,38,52]. Transmission of FIV across a mucosal surface may be enhanced by its ability to infect mucosal cells or by the capacity of cell-associated inocula to rapidly permeate the mucosa. Susceptible cells are abundant in the feline gastrointestinal tract as effector intraepithelial lymphocytes or lamina propria lymphocytes or in inductive sites such as Peyer's patches and lymphoid follicles [28]. Cell-associated vaginal inocula, but not cell-free inocula, appear to have the capacity to rapidly induce apoptosis of intraepithelial CD8+ lymphocytes of the intestinal tract, suggesting that the form of inoculum might influence the pathogenesis of mucosal infection [27]. Non-lymphoid cells such as follicle-associated intestinal epithelium become infected during transmission across the intestinal mucosa, although epithelial infection varies between studies [6,39]. Some populations of mucosal dendritic cells are susceptible to FIV infection, and these may migrate to the paracortex of lymph nodes soon after infection [39]. These populations differ from follicular dendritic cells in germinal centers, which bear FIV antigens but may not become truly infected [57]. Several molecules probably mediate the binding of FIV to dendritic cells. The best characterized is DC-SIGN, a C-type lectin that normally binds to ICAM-3 during interactions between dendritic cells and T cells [24]. DC SIGN mediates HIV infection of CD4+ T cells in trans by serving as a molecular chaperone for HIV as dendritic cells migrate from the intestinal mucosa to regional mesenteric lymph nodes and contact susceptible T cells [25]. Such a mechanism could explain the efficient transmission of cell-free FIV after mucosal inoculation [39]. Feline dendritic cells also appear to enhance the productive infection of both thymocytes and peripheral blood lymphocytes through a mechanism independent of DC-SIGN [59].
FIV isolates belonging to clade C have been extensively characterized in studies of mucosal transmission. Mucosally transmitted FIV-C (FIV-Pgmr), when administered by either oronasal, vaginal, or rectal routes, confers a spectrum of disease severity ranging from rapidly progressive to regressive [39]. A unifying lesion of the most pathogenic infections is the profound depletion of thymocytes and thymic dendritic cells [41]. An infectious molecular clone of FIV-C (FIV-C36) is thought to display enhanced properties for mucosal transmission, as illustrated by fetal-to-maternal transfer after experimental inoculation of nursing kittens [18]. Likewise, molecular clones of a clade B virus, FIV TM2, are infectious after vaginal exposure [32]. Within 1-2 days of experimental inoculation of oral or vaginal mucous membranes with clade C FIV, in situ hybridization identified infected CD3+ T cells and p55+ dendritic cells in the tonsillar, vaginal, or intestinal mucosa and in paracortical zones of regional lymph nodes [39].
==Pathogenesis==
==Pathogenesis==