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Equal contributions of feline immunodeficiency virus and coinfections to morbidity in African lions.

ABSTRACT: Feline immunodeficiency virus (FIV) is a pathogenic lentivirus related to human and simian immunodeficiency viruses that has been associated with AIDS-like pathologies in domestic and wild cats, as well as in hyenas. Despite known pathologies, progressive immunosuppression and ill health effects driven by these lentiviruses in association with other secondary infections remain understudied in free-ranging species. Here, the role of coinfections by gastrointestinal parasites and tick-borne hemoparasites for FIV disease progression was explored in 195 free-ranging African lions (Panthera leo) living in Kruger National Park (KNP), South Africa. Using statistical methodology, we evaluated the effects of FIV on a range of health indicators to explore how direct and indirect effects of FIV and associated coinfections align to determine lion health outcomes. Findings show direct negative effects of FIV on host immunity and nutritional status, and exacerbation of aggressive behaviors, conditions which may increase exposure/susceptibility to other secondary infections. When taken together, the contribution of coinfecting parasites to morbidity in lions is of similar magnitude as direct effects of FIV infection alone, suggesting that the particular coinfection assemblage may play a role in mediating disease progression within natural lion populations.

SUBMITTER: Broughton H

PROVIDER: S-EPMC8385399 | biostudies-literature | 2021 Dec

REPOSITORIES: biostudies-literature

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Equal contributions of feline immunodeficiency virus and coinfections to morbidity in African lions.

Broughton Heather H Govender Danny D Serrano Emmanuel E Shikwambana Purvance P Jolles Anna A

International journal for parasitology. Parasites and wildlife 20210819

Feline immunodeficiency virus (FIV) is a pathogenic lentivirus related to human and simian immunodeficiency viruses that has been associated with AIDS-like pathologies in domestic and wild cats, as well as in hyenas. Despite known pathologies, progressive immunosuppression and ill health effects driven by these lentiviruses in association with other secondary infections remain understudied in free-ranging species. Here, the role of coinfections by gastrointestinal parasites and tick-borne hemopa ...[more]

PMID: 34466379

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Project description:BackgroundFeline immunodeficiency virus (FIV) naturally infects multiple species of cat and is related to human immunodeficiency virus in humans. FIV infection causes AIDS-like disease and mortality in the domestic cat (Felis catus) and serves as a natural model for HIV infection in humans. In African lions (Panthera leo) and other exotic felid species, disease etiology introduced by FIV infection are less clear, but recent studies indicate that FIV causes moderate to severe CD4 depletion.ResultsIn this study, comparative genomic methods are used to evaluate the full proviral genome of two geographically distinct FIV subtypes isolated from free-ranging lions. Genome organization of FIVPle subtype B (9891 bp) from lions in the Serengeti National Park in Tanzania and FIVPle subtype E (9899 bp) isolated from lions in the Okavango Delta in Botswana, both resemble FIV genome sequence from puma, Pallas cat and domestic cat across 5' LTR, gag, pol, vif, orfA, env, rev and 3'LTR regions. Comparative analyses of available full-length FIV consisting of subtypes A, B and C from FIVFca, Pallas cat FIVOma and two puma FIVPco subtypes A and B recapitulate the species-specific monophyly of FIV marked by high levels of genetic diversity both within and between species. Across all FIVPle gene regions except env, lion subtypes B and E are monophyletic, and marginally more similar to Pallas cat FIVOma than to other FIV. Sequence analyses indicate the SU and TM regions of env vary substantially between subtypes, with FIVPle subtype E more related to domestic cat FIVFca than to FIVPle subtype B and FIVOma likely reflecting recombination between strains in the wild.ConclusionThis study demonstrates the necessity of whole-genome analysis to complement population/gene-based studies, which are of limited utility in uncovering complex events such as recombination that may lead to functional differences in virulence and pathogenicity. These full-length lion lentiviruses are integral to the advancement of comparative genomics of human pathogens, as well as emerging disease in wild populations of endangered species.

Project description:Feline immunodeficiency virus (FIV) Vif protein counteracts feline APOBEC3s (FcaA3s) restriction factors by inducing their proteasomal degradation. The functional domains in FIV Vif for interaction with FcaA3s are poorly understood. Here, we have identified several motifs in FIV Vif that are important for selective degradation of different FcaA3s. Cats (Felis catus) express three types of A3s: single-domain A3Z2, single-domain A3Z3, and double-domain A3Z2Z3. We proposed that FIV Vif would selectively interact with the Z2 and the Z3 A3s. Indeed, we identified two N-terminal Vif motifs (12LF13 and 18GG19) that specifically interacted with the FcaA3Z2 protein but not with A3Z3. In contrast, the exclusive degradation of FcaA3Z3 was regulated by a region of three residues (M24, L25, and I27). Only a FIV Vif carrying a combination of mutations from both interaction sites lost the capacity to degrade and counteract FcaA3Z2Z3. However, alterations in the specific A3s interaction sites did not affect the cellular localization of the FIV Vif protein and binding to feline A3s. Pulldown experiments demonstrated that the A3 binding region localized to FIV Vif residues 50 to 80, outside the specific A3 interaction domain. Finally, we found that the Vif sites specific to individual A3s are conserved in several FIV lineages of domestic cat and nondomestic cats, while being absent in the FIV Vif of pumas. Our data support a complex model of multiple Vif-A3 interactions in which the specific region for selective A3 counteraction is discrete from a general A3 binding domain.ImportanceBoth human immunodeficiency virus (HIV) and feline immunodeficiency virus (FIV) Vif proteins counteract their host's APOBEC3 restriction factors. However, these two Vif proteins have limited sequence homology. The molecular interaction between FIV Vif and feline APOBEC3s are not well understood. Here, we identified N-terminal FIV Vif sites that regulate the selective interaction of Vif with either feline APOBEC3Z2 or APOBEC3Z3. These specific Vif sites are conserved in several FIV lineages of domestic cat and nondomestic cats, while being absent in FIV Vif from puma. Our findings provide important insights for future experiments describing the FIV Vif interaction with feline APOBEC3s and also indicate that the conserved feline APOBEC3s interaction sites of FIV Vif allow FIV transmissions in Felidae.

Project description:Approximately 5% of cats in animal shelters in the United States test positive for either feline leukemia virus (FeLV) or feline immunodeficiency virus (FIV), which translates to more than 100,000 positive cats managed by shelters each year. Little is known about the current status of retroviral management in animal shelters, particularly in regions burdened by chronic pet overpopulation and high shelter admissions, such as the southern United States. The purpose of this study was to describe feline retroviral management in Florida shelters. Shelters were surveyed on practices including selection of cats for testing, diagnostic techniques, and outcome options for cats with positive test results. Responses were received from 139 of 153 animal shelters known to admit cats, including 55 municipal shelters (40%), 70 private shelters (50%), and 14 private shelters with municipal contracts (10%). A total of 115 shelters (83%) performed at least some testing, most using combination point-of-care devices for simultaneous FeLV antigen and FIV antibody screening. Of shelters that performed any testing, 56 (49%) tested all cats for FeLV and 52 (45%) tested all cats for both FeLV and FIV. The most common reason for testing was screening adoptable cats (108 shelters; 94%) and cats available for transfer to other organizations (78; 68%). Testing cats in trap-neuter-return/return-to-field programs was least common (21; 18%). Most common outcome options for positive cats included adoption (74; 64%), transfer (62; 54%), and euthanasia (49; 43%). Euthanasia following a positive test result was more common for cats with FeLV (49; 43%) than for cats with FIV (29; 25%) and was more common in municipal shelters, rural shelters, shelters taking in <500 cats a year, and shelters with overall live outcome rates for cats <70%. Although Florida shelter compliance with national guidelines for identification and management of FeLV and FIV positive cats was variable, most had live outcome options for at least some of their cats with positive test results. Increased access to training and practical programmatic tools may help more shelters implement cost-effective testing protocols, reduce risk for transmission to other cats, and support the best outcomes for this vulnerable population of cats.

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Equal contributions of feline immunodeficiency virus and coinfections to morbidity in African lions.

Publications

Equal contributions of feline immunodeficiency virus and coinfections to morbidity in African lions.

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