Viruses as indicators of contemporary host dispersal and phylogeography: an example of feline immunodeficiency virus (FIVPle ) in free-ranging African lion (Panthera leo).

Measuring contemporary dispersal in highly mobile terrestrial species is challenging, especially when species are characterized by low levels of population differentiation. Directly transmitted viruses can be used as a surrogate for traditional methods of tracking host movement. Feline immunodeficiency virus (FIV) is a species-specific lentivirus, which has an exceptionally high mutation rate and circulates naturally in wild felids. Using samples derived from 35 lion (Panthera leo) prides, we tested the prediction that FIV in lions (FIVPle ) can be used to track the dispersal of individuals between prides. As FIVPle subtypes are geographically structured throughout Africa, we predicted that this marker could be used to detect phylogeographic structure of lions at smaller spatial scales. Phylogenetic analyses of FIVPle pol-RT sequences showed that core pride members (females and subadults) shared evolutionary close viral lineages which differed from neighbouring core prides, whereas sequences from sexually mature males associated with the same pride were always the most divergent. In six instances, natal pride associations of divergent male lions could be inferred, on the assumption that FIVPle infections are acquired during early life stages. Congruence between the genetic pattern of FIV and pride structure suggests that vertical transmission plays an important role in lion FIV dynamics. At a fine spatial scale, significant viral geographic structuring was also detected between lions occurring north of the Olifants River within the Kruger National Park (KNP) and those occupying the southern and central regions. This pattern was further supported by phylogenetic analyses and the confinement of FIVPle subtype E to the northern region of KNP. The study provides new insights into the use of retroviral sequences to predict host dispersal and fine-scale contemporary geographic structure in a social felid species.

Pathogenesis of oral FIV infection.

Feline immunodeficiency virus (FIV) is the feline analogue of human immunodeficiency virus (HIV) and features many hallmarks of HIV infection and pathogenesis, including the development of concurrent oral lesions. While HIV is typically transmitted via parenteral transmucosal contact, recent studies prove that oral transmission can occur, and that saliva from infected individuals contains significant amounts of HIV RNA and DNA. While it is accepted that FIV is primarily transmitted by biting, few studies have evaluated FIV oral infection kinetics and transmission mechanisms over the last 20 years. Modern quantitative analyses applied to natural FIV oral infection could significantly further our understanding of lentiviral oral disease and transmission. We therefore characterized FIV salivary viral kinetics and antibody secretions to more fully document oral viral pathogenesis. Our results demonstrate that: (i) saliva of FIV-infected cats contains infectious virus particles, FIV viral RNA at levels equivalent to circulation, and lower but significant amounts of FIV proviral DNA; (ii) the ratio of FIV RNA to DNA is significantly higher in saliva than in circulation; (iii) FIV viral load in oral lymphoid tissues (tonsil, lymph nodes) is significantly higher than mucosal tissues (buccal mucosa, salivary gland, tongue); (iv) salivary IgG antibodies increase significantly over time in FIV-infected cats, while salivary IgA levels remain static; and, (v) saliva from naïve Specific Pathogen Free cats inhibits FIV growth in vitro. Collectively, these results suggest that oral lymphoid tissues serve as a site for enhanced FIV replication, resulting in accumulation of FIV particles and FIV-infected cells in saliva. Failure to induce a virus-specific oral mucosal antibody response, and/or viral capability to overcome inhibitory components in saliva may perpetuate chronic oral cavity infection. Based upon these findings, we propose a model of oral FIV pathogenesis and suggest alternative diagnostic modalities and translational approaches to study oral HIV infection.

Sexually transmitted infections and mate-finding Allee effects.

Infectious diseases can seriously impact dynamics of their host species. In this study, we model and analyze an interaction between a sexually transmitted infection and its animal host population affected by a mate-finding Allee effect. Since mating drives both host reproduction and infection transmission, the Allee effect shapes the transmission rate of the infection which we show takes a saturating form. Our model combining sexually transmitted infections with the mate-finding Allee effect in the host produces quite rich dynamics, including oscillations, several multistability regimes, and infection-induced host extinction. However, many of these complex patterns are restricted to a relatively narrow parameter range. We find that the host extinction occurs at intermediate levels of infection virulence, as well as for Allee effect strengths much lower than when the infection is absent. In both cases, a sequence of events comprising destabilization of an endemic equilibrium, growth of oscillation amplitude, and a heteroclinic bifurcation forms an underlying mechanism. We apply our model to the feline immunodeficiency virus (FIV) in domestic cats.

Seroprevalence of feline immunodeficiency virus (FIV) and feline leukemia virus (FeLV) in shelter cats on the island of Newfoundland, Canada.

Feline immunodeficiency virus (FIV) and feline leukemia virus (FeLV) are retroviruses found within domestic and wild cat populations. These viruses cause severe illnesses that eventually lead to death. Housing cats communally for long periods of time makes shelters at high risk for virus transmission among cats. We tested 548 cats from 5 different sites across the island of Newfoundland for FIV and FeLV. The overall seroprevalence was 2.2% and 6.2% for FIV and FeLV, respectively. Two sites had significantly higher seroprevalence of FeLV infection than the other 3 sites. Analysis of sequences from the FeLV env gene (envelope gene) from 6 positive cats showed that 4 fell within the FeLV subtype-A, while 2 sequences were most closely related to FeLV subtype-B and endogenous feline leukemia virus (en FeLV). Varying seroprevalence and the variation in sequences at different sites demonstrate that some shelters are at greater risk of FeLV infections and recombination can occur at sites of high seroprevalence.

Le virus de l'immunodéficience féline (FIV) et le virus de la leucémie féline (FeLV) sont des rétrovirus retrouvés chez les populations de chats domestiques et sauvages. Ces virus causent des maladies sévères qui éventuellement mènent à la mort. L'hébergement de chats de façon communautaire pendant de longues périodes rend les refuges à risque élevé pour la transmission du virus parmi les chats. Nous avons testé 548 chats provenant de cinq sites différents à travers l'ile de Terre-Neuve pour FIV et FeLV. La séroprévalence globale était de 2,2 % et 6,2 % pour FIV et FeLV, respectivement. Deux sites avaient une séroprévalence significativement plus élevée d'infection par FeLV que les trois autres sites. L'analyse des séquences du gène env de FeLV (gène de l'enveloppe) provenant de six chats positifs a montré que quatre appartenaient au sous-type A de FeLV, alors que deux séquences étaient plus apparentées au sous-type B de FeLV et du virus endogène de la leucémie féline (en FeLV). Une séroprévalence variable et la variation dans les séquences à différents sites démontrent que certains refuges sont à risque plus élevé d'infections par FeLV et que de la recombinaison peut survenir aux sites avec une séroprévalence élevée.(Traduit par Docteur Serge Messier).

Natural transmission of feline immunodeficiency virus from infected queen to kitten.

BACKGROUND: Feline immunodeficiency virus (FIV) is a naturally occurring lentivirus that infects cats. The primary mode of transmission occurs through bite wounds, and other routes are difficult to observe in nature. FINDINGS: The purpose of this study was to evaluate FIV transmission from queen to kitten in a colony of naturally infected stray cats. With this aim, a queen was monitored over a period of three years. A blood sample was taken to amplify and sequence gag, pol and env regions of the virus from the queen, two kittens and other cats from the colony. CONCLUSION: Phylogenetic analysis showed evidence of queen to kitten transmission.

Integration of immunodeficiency virus in oocytes via intracytoplasmic injection: possible but extremely unlikely.

OBJECTIVE: To determine if human oocytes can be infected with HIV-1 via intracytoplasmic injection and to determine the infection threshold. DESIGN: Twenty-eight donated immature and unfertilized human oocytes from HIV-negative women were injected with 4 × 10(4) HIV-1 virions and 13 oocytes were used as uninjected controls. To determine the infection threshold, 543 cat oocytes were injected with 4 × 10(4), 4 × 10(2), or 40 copies of feline immunodeficiency virus (FIV) and 376 oocytes were used as controls. SETTING: Academic hospital. PATIENT(S)/ANIMAL(S): Donated immature human oocytes and mature cat oocytes. INTERVENTION(S): Injection with HIV-1 or FIV. MAIN OUTCOME MEASURE(S): Viral integration as measured by fluorescent in situ hybridization with HIV-1-specific probes or by nested FIV polymerase chain reaction. RESULT(S): We detected viral integration in three of 28 (11%) human oocytes injected with 4 × 10(4) copies of HIV-1. When injected with high dose FIV (4 × 10(4) copies) 16%-49% of cat oocytes showed viral integration. This decreased to 2%-7% and 0.6%-1.8% when an intermediate (4 × 10(2) copies) or low (40 copies) dose was injected, respectively. CONCLUSION(S): Human and cat oocytes can be infected with HIV-1 and FIV respectively, when injected with high amounts of virus. The probability of viral integration is extremely low when small amounts of virus particles are injected. Taking into account the small volume injected during intracytoplasmic injection, the chances of viral integration are 0.00002%.

Gene flow and pathogen transmission among bobcats (Lynx rufus) in a fragmented urban landscape.

Urbanization can result in the fragmentation of once contiguous natural landscapes into a patchy habitat interspersed within a growing urban matrix. Animals living in fragmented landscapes often have reduced movement among habitat patches because of avoidance of intervening human development, which potentially leads to both reduced gene flow and pathogen transmission between patches. Mammalian carnivores with large home ranges, such as bobcats (Lynx rufus), may be particularly sensitive to habitat fragmentation. We performed genetic analyses on bobcats and their directly transmitted viral pathogen, feline immunodeficiency virus (FIV), to investigate the effects of urbanization on bobcat movement. We predicted that urban development, including major freeways, would limit bobcat movement and result in genetically structured host and pathogen populations. We analysed molecular markers from 106 bobcats and 19 FIV isolates from seropositive animals in urban southern California. Our findings indicate that reduced gene flow between two primary habitat patches has resulted in genetically distinct bobcat subpopulations separated by urban development including a major highway. However, the distribution of genetic diversity among FIV isolates determined through phylogenetic analyses indicates that pathogen genotypes are less spatially structured-exhibiting a more even distribution between habitat fragments. We conclude that the types of movement and contact sufficient for disease transmission occur with enough frequency to preclude structuring among the viral population, but that the bobcat population is structured owing to low levels of effective bobcat migration resulting in gene flow. We illustrate the utility in using multiple molecular markers that differentially detect movement and gene flow between subpopulations when assessing connectivity.

Feline immunodeficiency virus: disease association versus causation in domestic and nondomestic felids.

Feline immunodeficiency virus (FIV) is an important infection in both domestic and nondomestic cats. Although many studies have provided insight into FIV pathophysiology and immunologic responses to infection in cats, questions remain regarding the association of FIV with specific disease syndromes. For many diseases, both association and causation of disease with FIV remain to be confirmed and clarified. The use of experimental infection models is unlikely to yield answers about naturally infected domestic cats and is not feasible in nondomestic felids, many of which are endangered species. Researches might consider further study of naturally occurring disease with an emphasis on confirming which diseases have a likely association with FIV.

Prior mucosal exposure to heterologous cells alters the pathogenesis of cell-associated mucosal feline immunodeficiency virus challenge.

BACKGROUND: Several lines of research suggest that exposure to cellular material can alter the susceptibility to infection by HIV-1. Because sexual contact often includes exposure to cellular material, we hypothesized that repeated mucosal exposure to heterologous cells would induce an immune response that would alter the susceptibility to mucosal infection. Using the feline immunodeficiency virus (FIV) model of HIV-1 mucosal transmission, the cervicovaginal mucosa was exposed once weekly for 12 weeks to 5,000 heterologous cells or media (control) and then cats were vaginally challenged with cell-associated or cell-free FIV. RESULTS: Exposure to heterologous cells decreased the percentage of lymphocytes in the mucosal and systemic lymph nodes (LN) expressing L-selectin as well as the percentage of CD4+ CD25+ T cells. These shifts were associated with enhanced ex-vivo proliferative responses to heterologous cells. Following mucosal challenge with cell-associated, but not cell-free, FIV, proviral burden was reduced by 64% in cats previously exposed to heterologous cells as compared to media exposed controls. CONCLUSIONS: The pathogenesis and/or the threshold for mucosal infection by infected cells (but not cell-free virus) can be modulated by mucosal exposure to uninfected heterologous cells.

Risk analysis of feline immunodeficiency virus infection in Tsushima leopard cats (Prionailurus bengalensis euptilurus) and domestic cats using a geographic information system.

In this study, based on the data from FIV screening surveys of captive cats conducted by the Kyushu Veterinary Union and collaborators as part of the infection control program for Tsushima leopard cats (Prionailurus bengalensis euptilurus), we elucidated the spatial distribution of FIV-positive individuals among leopard cats and domestic cats using a geographic information system. Data from FIV screening surveys carried out among 86 leopard cats (1996-2006) and 713 captive domestic cats (2001-2006) were used for analysis. The analysis results were then spatially layered with the population density of leopard cats and that of captive domestic cats estimated from the number of households and used for assessment of FIV infection risk in each area. The prevalence rates of FIV were 3% (3/86) in leopard cats in Kami-shima, 13.6% (38/280) in domestic cats in Kami-shima and 10.6% (46/433) in domestic cats in Shimo-shima. The distribution of FIV on Tsushima Island was not uniform; on Kami-shima Island, FIV-positive domestic cats were concentrated in particular areas. We also performed risk analysis based on the population density of leopard cats, the prevalence rate of FIV among domestic cats in each area and the estimated population density of captive domestic cats and identified high FIV infection risk areas. All FIV-positive leopard cats were found in the identified high FIV infection risk areas.

Restrictions to cross-species transmission of lentiviral infection gleaned from studies of FIV.

More than 40 species of primates and over 20 species of cats harbor antibodies that sero-react to lentiviral antigens. In nearly all cases where viral genetic analysis has been conducted, each host species is infected with a unique lentivirus. Though lentivirus clades within a species can be substantially divergent, they are typically monophyletic within that species. A notable significant departure from this observation is apparent cross-species transmission of FIV between bobcats (Lynx rufus) and pumas (Puma concolor) in Southern California that has occurred at least three times; evidence from one bobcat sequence suggests this cross-over may have also occurred in Florida between bobcats and the endangered Florida panther. Several other isolated reports demonstrate cross-species transmission of FIV isolates among captive animals housed in close proximity, and it is well established that HIV-1 and HIV-2 arose from human contact with SIV-infected non-human primates. Using an experimental model, we have determined that domestic cats (Felis catus) are susceptible to FIVs originating from pumas or lions. While infections are initially replicative, and animals seroconvert, within a relatively short period of time circulating virus is reduced to nearly undetectable levels in a majority of animals. This diminution of viral load is proportional to initial viral peak. Although viral reservoirs can be identified in gastrointestinal tissues, most viral genomes recovered peripherally are highly mutated, suggesting that the non-adapted host successfully inhibits normal viral replication, leading to replication incompetent viral progeny. Mechanisms possible for such restriction of cross-species infections in natural settings include: (1) Lack of contact conducive to lentiviral transmission between infected and shedding animals of different species; (2) Lack of suitable receptor repertoire to allow viral entry to susceptible cells of a new species; (3) Cellular machinery in the new host sufficiently divergent from the primary host to support viral replication (i.e. passive unfacilitated viral replication); (4) Intracellular restriction mechanisms present in the new host that is able to limit viral replication (i.e. active interrupted viral replication. These include factors that limit uncoating, replication, packaging, and virion release); (5) Unique ability of new host to raise sterilizing adaptive immunity, resulting in aborted infection and inability to spread infections among con-specifics; or (6) Production of defective or non-infectious viral progeny that lack cellular cofactors to render them infectious to con-specifics (i.e. particles lacking appropriate cellular components in viral Env to render them infectious to other animals of the same species). Data to support or refute the relative importance of each of these possibilities is described in this review. Insights based on our in vivo cross-species model suggest intracellular restriction mechanisms effectively inhibit rapid inter-specific transmission of lentiviruses. Further, limited contact both within and between species in natural populations is highly relevant to limiting the opportunity for spread of FIV strains. Studies of naturally occurring SIV and innate host restriction systems suggest these same two mechanisms are significant factors inhibiting widespread cross-species transmission of lentiviruses among primate species as well.

Modelling disease introduction as biological control of invasive predators to preserve endangered prey.

Invasive species are a significant cause of bio-diversity loss particularly in island ecosystems. It has been suggested to release pathogenic parasites as an efficient control measure of these mostly immune-naïve populations. In order to explore the potential impacts of such bio-control approach, we construct and investigate mathematical models describing disease dynamics in a host population that acts as a predator embedded in a simple food chain. The consequences of Feline Immunodeficiency Virus (FIV) introduction into a closed ecosystem are addressed using a bi-trophic system, comprising an indigenous prey (birds) and an introduced predator (cats). Our results show that FIV is unlikely to fully eradicate cats on sub-Antarctic islands, but it can be efficient in depressing their population size, allowing for the recovery of the endangered prey. Depending on the ecological setting and disease transmission mode (we consider proportionate mixing as well as mass action), successful pathogen invasion can induce population oscillations that are not possible in the disease-free predator-prey system. These fluctuations can be seen as a mixed blessing from a management point of view. On the one hand, they may increase the extinction risk of the birds. On the other hand, they provide an opportunity to eradicate cats more easily in combination with other methods such as trapping or culling.

Feline immunodeficiency. ABCD guidelines on prevention and management.

OVERVIEW: Feline immunodeficiency virus (FIV) is a retrovirus closely related to human immunodeficiency virus. Most felids are susceptible to FIV, but humans are not. Feline immunodeficiency virus is endemic in domestic cat populations worldwide. The virus loses infectivity quickly outside the host and is susceptible to all disinfectants. INFECTION: Feline immunodeficiency virus is transmitted via bites. The risk of transmission is low in households with socially well-adapted cats. Transmission from mother to kittens may occur, especially if the queen is undergoing an acute infection. Cats with FIV are persistently infected in spite of their ability to mount antibody and cell-mediated immune responses. DISEASE SIGNS: Infected cats generally remain free of clinical signs for several years, and some cats never develop disease, depending on the infecting isolate. Most clinical signs are the consequence of immunodeficiency and secondary infection. Typical manifestations are chronic gingivostomatitis, chronic rhinitis, lymphadenopathy, weight loss and immune-mediated glomerulonephritis. DIAGNOSIS: Positive in-practice ELISA results obtained in a low-prevalence or low-risk population should always be confirmed by a laboratory. Western blot is the 'gold standard' laboratory test for FIV serology. PCR-based assays vary in performance. DISEASE MANAGEMENT: Cats should never be euthanased solely on the basis of an FIV-positive test result. Cats infected with FIV may live as long as uninfected cats, with appropriate management. Asymptomatic FIV-infected cats should be neutered to avoid fighting and virus transmission. Infected cats should receive regular veterinary health checks. They can be housed in the same ward as other patients, but should be kept in individual cages. VACCINATION RECOMMENDATIONS: At present, there is no FIV vaccine commercially available in Europe. Potential benefits and risks of vaccinating FIV-infected cats should be assessed on an individual cat basis. Needles and surgical instruments used on FIV-positive cats may transmit the virus to other cats, so strict hygiene is essential.

Maternal hematological and virological characteristics during early feline immunodeficiency virus (FIV) infection of cats as predictors of fetal infection and reproductive outcome at early gestation.

The FIV-infected cat is a small animal model for HIV mother-to-child transmission (MTCT) because the two lentiviruses are biologically related and produce similar clinical syndromes. Both viruses are vertically transmissible and may negatively impact reproductive outcome. Maternal hematological and virological parameters are predictors of MTCT in HIV-infected women. Our purpose was to determine whether similar maternal characteristics during early pregnancy in FIV-infected cats influence pregnancy outcome. We inoculated 10 cats with FIV-B-2542; 10 cats were uninoculated. We quantified longitudinal CD4:CD8 T cell ratios, proviral load, and plasma viremia, monitored longitudinal serostatus, and documented clinical and reproductive outcome during early pregnancy. Inoculated queens were seropositive and provirus positive by week 4 post-infection (p.i.). CD4:CD8 ratios were depressed in the infected group by month 3.5 p.i. Proviral load was variable in the animals throughout the course of infection; plasma viremia was below the level of detection in all animals. Reduced litter sizes and increased fetal demise occurred in infected queens. Viral RNA, but not proviral DNA, was detected in representative placentas (14 of 14; 100%) and fetuses (12 of 14; 86%) collected from infected queens. However, maternal virological and hematological characteristics did not correlate either positively or negatively with reproductive outcome.

The Allee effect and infectious diseases: extinction, multistability, and the (dis-)appearance of oscillations.

Infectious diseases that affect their host on a long timescale can regulate the host population dynamics. Here we show that a strong Allee effect can lead to complex dynamics in simple epidemic models. Generally, the Allee effect renders a population bistable, but we also identify conditions for tri- or monostability. Moreover, the disease can destabilize endemic equilibria and induce sustained oscillations. These disappear again for high transmissibilities, with eventually vanishing host population. Disease-induced extinction is thus possible for density-dependent transmission and without any alternative reservoirs. The overall complexity suggests that the system is very sensitive to perturbations and control methods, even in parameter regions with a basic reproductive ratio far beyond R(0) = 1. This may have profound implications for biological conservation as well as pest management. We identify important threshold quantities and attribute the dynamical behavior to the joint interplay of a strong Allee effect and infection.

Expression of CD134 and CXCR4 mRNA in term placentas from FIV-infected and control cats.

Feline immunodeficiency virus (FIV) causes a natural infection of domestic cats that resembles HIV-1 in pathogenesis and disease progression. Feline AIDS is characterized by depression of the CD4+ T cell population and fatal opportunistic infections. Maternal-fetal transmission of FIV readily occurs under experimental conditions, resulting in infected viable kittens and resorbed or arrested fetal tissues. Although both FIV and HIV use the chemokine receptor CXCR4 as a co-receptor, FIV does not utilize CD4 as the primary receptor. Rather, CD134 (OX40), a T cell activation antigen and co-stimulatory molecule, is the primary receptor for FIV. We hypothesized that placental expression of CD134 and CXCR4 may render the placenta vulnerable to FIV infection, possibly facilitating efficient vertical transmission of FIV, and impact pregnancy outcome. The purpose of this project was to quantify the relative expression of CD134 and CXCR4 mRNA from the term placentas of three groups of cats: uninfected queens producing viable offspring, experimentally-infected queens producing only viable offspring, and experimentally-infected queens producing viable offspring among mostly non-viable fetuses. Total RNA was extracted from term placental tissues from all groups of cats. Real-time one-step reverse transcriptase-PCR was used to measure gene expression. The FIV receptors CD134 and CXCR4 were expressed in all late term feline placental tissues. Placentas from FIV-infected queens producing litters of only viable offspring expressed more CD134 and CXCR4 mRNA than those from uninfected queens, suggesting that infection may cause upregulation of the receptors. On the other hand, placentas from FIV-infected cats with non-successful pregnancies expressed similar levels of CD134 mRNA and slightly less CXCR4 mRNA than those from uninfected queens. Thus, it appears that cells expressing these receptors may play a role in pregnancy maintenance.

Immunopathogenesis of feline immunodeficiency virus infection in the fetal and neonatal cat.

The global incidence of pediatric HIV infection is estimated at 2.3 million children, most acquiring the infection from their mothers in utero, peripartum, or postpartum. Pediatric HIV infection typically causes a rapidly progressive disease when compared with adult infection, due in part to the profound susceptibility of the neonatal thymus to productive infection or degenerative changes. Failed production of naive T-lymphocytes further limits the success of antiviral therapy to restore immunologic function. In this review, we explore the use of feline immunodeficiency virus (FIV) infection of domestic cats as an animal model for pediatric HIV infection. Cats infected with FIV represent the smallest host of a naturally occurring lentivirus, and the immunodeficiency syndrome elicited by FIV infection is similar to that of HIV-AIDS. The feline-FIV model uniquely reproduces several key aspects of immunosuppressive lentivirus infection of the thymus, allowing investigators to define viral determinants of pathogenicity, influence of host age on disease outcome, and therapeutic strategies to restore thymus function.

A diffusive SI model with Allee effect and application to FIV.

A minimal reaction-diffusion model for the spatiotemporal spread of an infectious disease is considered. The model is motivated by the Feline Immunodeficiency Virus (FIV) which causes AIDS in cat populations. Because the infected period is long compared with the lifespan, the model incorporates the host population growth. Two different types are considered: logistic growth and growth with a strong Allee effect. In the model with logistic growth, the introduced disease propagates in form of a travelling infection wave with a constant asymptotic rate of spread. In the model with Allee effect the spatiotemporal dynamics are more complicated and the disease has considerable impact on the host population spread. Most importantly, there are waves of extinction, which arise when the disease is introduced in the wake of the invading host population. These waves of extinction destabilize locally stable endemic coexistence states. Moreover, spatially restricted epidemics are possible as well as travelling infection pulses that correspond either to fatal epidemics with succeeding host population extinction or to epidemics with recovery of the host population. Generally, the Allee effect induces minimum viable population sizes and critical spatial lengths of the initial distribution. The local stability analysis yields bistability and the phenomenon of transient epidemics within the regime of disease-induced extinction. Sustained oscillations do not exist.

Mutations in feline immunodeficiency (FIV) virus envelope gene V3-V5 regions in FIV-infected cats.

The envelope (Env) gene V3-V5 regions of the feline immunodeficiency virus (FIV) encode the neutralizing epitopes. Since mutations in these regions induce resistance to viral neutralizing antibodies, they may influence the effects of vaccines. To examine the in vivo mutation rate in these regions, we cloned cDNA for the Env gene V3-V5 regions from the PBMC of experimentally FIV-infected cats, and compared the deduced amino acid sequences. Blood or plasma from an FIV Shizuoka strain-infected cat was inoculated into a second group of SPF cats, and their blood or plasma was inoculated into the third group. The amino acid sequence encoded by the viral gene of the first cat was compared with those encoded by the viral genes of a total of eight cats in the second and third groups (two and six cats, respectively). The amino acid sequences in two cats in the second and third groups were 100% homologous and in one cat in the third group was 98.3% homologous to that in the first infected cat. Five cats had the same sequence, which was 97.8% homologous to that in the first infected cat. Three kittens, born 2 months after the inoculation of the FIV Aomori-2 strain into the mother cat, were anti-FIV negative at 4 weeks after birth, but became seropositive at 33 weeks after birth, confirming FIV infection. Comparison of the encoded amino acid sequences of the viral gene in two cats at 48 weeks after birth showed 100% homology to that of the virus inoculated into the mother cat, and the remaining one cat had a single residue substitution, resulting in 99.4% homology. These results suggest that the FIV Env gene V3-V5 regions are stably maintained for at least 1-2 years after infection.

Placental immunopathology and pregnancy failure in the FIV-infected cat.

Placental HIV infections frequently result in infected babies or miscarriage. Aberrant placental cytokine expression during HIV infections may facilitate transplacental viral transmission or pregnancy perturbation. The feline immunodeficiency virus (FIV)-infected cat is a model for HIV infections due to similarities in biology and clinical disease. The purpose of this study was to evaluate placental immunomodulator expression and reproductive outcome using the FIV-infected cat model. Kittens were cesarean delivered from FIV-B-2542-infected and control queens near term; placental and fetal tissues were collected. Real-time RT-PCR was used to measure expression of representative placental Th1 cytokines, interleukin-1beta (IL-1beta) and interferon-gamma (IFN-gamma), a Th2 cytokine, IL-10, and chemokine receptor CXCR4. On average, control queens delivered 3.8 kittens/litter; 1 of 31 kittens (3.2%) was non-viable. FIV-infected queens produced 2.7 kittens/litter; 15 of 25 concepti (60%) were non-viable. FIV was detected in 14 of 15 placentas (93%) and 21 of 22 fetuses (95%) using PCR. Placental immunomodulator expression did not differ significantly when placentas from infected cats were compared to those of control cats. However, elevated expression of Th1 cytokines and increased Th1/Th2 ratios (IL-1beta/IL-10) occurred in placentas from resorptions. Therefore, increased placental Th1 cytokine expression was associated with pregnancy failure in the FIV-infected cat.