A comprehensive investigation on the interplay between feline APOBEC3Z3 proteins and feline immunodeficiency virus Vif proteins

As the hosts of lentiviruses, almost 40 species of felids (the family Felidae) are distributed around the world, and more than 20 feline species are positive for feline immunodeficiency virus (FIV), a lineage of lentiviruses. These observations suggest that FIVs globally infect a variety of feline species through multiple cross-species transmission events during million years history. Cellular restriction factors potentially inhibit lentiviral replication and limit cross-species lentiviral transmission, and cellular APOBEC3 deaminases are known as a potent restriction factor. In contrast, lentiviruses have evolutionary acquired viral infectivity factor (Vif) to neutralize APOBEC3-mediated antiviral effect. Because the APOBEC3-Vif interaction is strictly specific for viruses and their hosts, a comprehensive investigation focusing on Vif-APOBEC3 interplay can provide clues that will elucidate the roles of this virus-host interplay on cross-species transmission of lentiviruses. Here we performed a comprehensive investigation with 144 patterns of the round-robin test using 18 feline APOBEC3Z3, an antiviral APOBEC3 gene in felid, and 8 FIV Vifs and derived a matrix showing the interplay between feline APOBEC3Z3 and FIV Vif. We particularly focused on the interplay between the APOBEC3Z3 of three felids (domestic cat, ocelot and Asian golden cat) and an FIV Vif (strain Petaluma), and revealed that residues 65 and 66 of the APOBEC3Z3 protein of multiple felids are responsible for the counteraction triggered by FIV Petaluma Vif. Altogether, our findings can be a clue to elucidate not only the scenarios of the cross-species transmissions of FIVs in felids but also the evolutionary interaction between mammals and lentiviruses. Importance Most of the emergence of new virus infection is originated from the cross-species transmission of viruses. The fact that some virus infections are strictly specific for the host species indicates that certain "species barriers" in the hosts restrict cross-species jump of viruses, while viruses have evolutionary acquired their own "arms" to overcome/antagonize/neutralize these hurdles. Therefore, understanding of the molecular mechanism leading to successful cross-species viral transmission is crucial for considering the menus of the emergence of novel pathogenic viruses. In the field of retrovirology, APOBEC3-Vif interaction is a well-studied example of the battles between hosts and viruses. Here we determined the sequences of 11 novel feline APOBEC3Z3 genes and demonstrated that all 18 different feline APOBEC3Z3 proteins tested exhibit anti-FIV activity. Our comprehensive investigation focusing on the interplay between feline APOBEC3 and FIV Vif can be a clue to elucidate the scenarios of the cross-species transmissions of FIVs in felids.

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Microsphere immunoassay for the detection of cytokines in domestic cat (Felis catus) plasma: Elevated IL-12/23 in acute feline immunodeficiency virus infections

Veterinary Immunology and Immunopathology ◽

10.1016/j.vetimm.2012.01.005 ◽

2012 ◽

Vol 145 (3-4) ◽

pp. 604-610 ◽

Cited By ~ 4

Author(s):

Britta A. Wood ◽

Ryan M. Troyer ◽

Julie A. TerWee ◽

Sue VandeWoude

Keyword(s):

Feline Immunodeficiency Virus ◽

Felis Catus ◽

Domestic Cat ◽

Virus Infections ◽

Immunodeficiency Virus ◽

Microsphere Immunoassay

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Vif of Feline Immunodeficiency Virus from Domestic Cats Protects against APOBEC3 Restriction Factors from Many Felids

Journal of Virology ◽

10.1128/jvi.00209-10 ◽

2010 ◽

Vol 84 (14) ◽

pp. 7312-7324 ◽

Cited By ~ 42

Author(s):

Jörg Zielonka ◽

Daniela Marino ◽

Henning Hofmann ◽

Naoya Yuhki ◽

Martin Löchelt ◽

...

Keyword(s):

Feline Immunodeficiency Virus ◽

Domestic Cat ◽

Moderate Degree ◽

Restriction Factors ◽

Cytidine Deaminases ◽

Immunodeficiency Virus ◽

Specific Restriction ◽

Species Specific ◽

Vif Protein ◽

Hiv 1

ABSTRACT To get more insight into the role of APOBEC3 (A3) cytidine deaminases in the species-specific restriction of feline immunodeficiency virus (FIV) of the domestic cat, we tested the A3 proteins present in big cats (puma, lion, tiger, and lynx). These A3 proteins were analyzed for expression and sensitivity to the Vif protein of FIV. While A3Z3s and A3Z2-Z3s inhibited Δvif FIV, felid A3Z2s did not show any antiviral activity against Δvif FIV or wild-type (wt) FIV. All felid A3Z3s and A3Z2-Z3s were sensitive to Vif of the domestic cat FIV. Vif also induced depletion of felid A3Z2s. Tiger A3s showed a moderate degree of resistance against the Vif-mediated counter defense. These findings may imply that the A3 restriction system does not play a major role to prevent domestic cat FIV transmission to other Felidae. In contrast to the sensitive felid A3s, many nonfelid A3s actively restricted wt FIV replication. To test whether VifFIV can protect also the distantly related human immunodeficiency virus type 1 (HIV-1), a chimeric HIV-1.VifFIV was constructed. This HIV-1.VifFIV was replication competent in nonpermissive feline cells expressing human CD4/CCR5 that did not support the replication of wt HIV-1. We conclude that the replication of HIV-1 in some feline cells is inhibited only by feline A3 restriction factors and the absence of the appropriate receptor or coreceptor.

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Feline Immunodeficiency Virus Vif N-Terminal Residues Selectively Counteract Feline APOBEC3s

Journal of Virology ◽

10.1128/jvi.01593-16 ◽

2016 ◽

Vol 90 (23) ◽

pp. 10545-10557 ◽

Cited By ~ 7

Author(s):

Qinyong Gu ◽

Zeli Zhang ◽

Lucía Cano Ortiz ◽

Ana Cláudia Franco ◽

Dieter Häussinger ◽

...

Keyword(s):

Feline Immunodeficiency Virus ◽

Cellular Localization ◽

Single Domain ◽

Domestic Cat ◽

Restriction Factors ◽

Interaction Domain ◽

Content Type ◽

Interaction Sites ◽

Immunodeficiency Virus ◽

Vif Protein

ABSTRACTFeline 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 inFelidae.

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Prevalence of Feline Immunodeficiency Virus and Toxoplasma gondii in Feral Cats on St. Kitts, West Indies

Veterinary Sciences ◽

10.3390/vetsci8020016 ◽

2021 ◽

Vol 8 (2) ◽

pp. 16

Author(s):

Xinyu Chi ◽

Kexin Fang ◽

Liza Koster ◽

Jevan Christie ◽

Chaoqun Yao

Keyword(s):

Toxoplasma Gondii ◽

Feline Immunodeficiency Virus ◽

Odds Ratio ◽

Protozoan Parasite ◽

Domestic Cat ◽

Feral Cats ◽

Immunodeficiency Virus ◽

Polymerase Chain ◽

One Year

Toxoplasma gondii (T. gondii) is a cosmopolitan protozoan parasite that infects all warm-blooded species including humans. The definitive hosts of T. gondii are felid vertebrates including the domestic cat. Domestic cats shed oocysts for approximately two weeks in their feces after the primary infection. It has been shown that feline immunodeficiency virus (FIV) positive cats have a higher prevalence of and a higher titer of antibodies to T. gondii than those of FIV-negative cats. The main purposes of this study were to determine FIV prevalence and to investigate the oocysts shedding in FIV-positive and FIV-negative feral cats on St. Kitts. Fecal samples were collected from feral cats while their FIV statues were determined using a commercial SNAP kit. Total fecal DNA of each cat was tested for the presence of T. gondii DNA using a polymerase chain reaction (PCR) consistently detecting one genome equivalent. A FIV-positive status was detected in 18 of 105 (17.1%, 95% confidence interval (CI): 9.9%−24.3%) feral cats sampled. Furthermore, males were three times more likely to be FIV positive than females (p = 0.017) with an odds ratio of 3.93 (95% CI: 1.20–12.89). Adults were found to have at least twice the prevalence of FIV compared to cats younger than one year of age (p = 0.056) with an odds ratio of 3.07 (95% CI: 0.94–10.00). Toxoplasma gondii DNA was not detected in the feces of any of the 18 FIV-positive (95% CI: 0%−0.18%) and 87 FIV-negative cats (95% CI: 0%−0.04%). A follow-up study with a much bigger sample size is needed to prove or disprove the hypothesis that FIV-positive cats have a higher prevalence of shedding T. gondii oocysts than FIV-negative cats.

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Cellular Restriction Factors of Feline Immunodeficiency Virus

Viruses ◽

10.3390/v3101986 ◽

2011 ◽

Vol 3 (10) ◽

pp. 1986-2005 ◽

Cited By ~ 13

Author(s):

Jörg Zielonka ◽

Carsten Münk

Keyword(s):

Feline Immunodeficiency Virus ◽

Restriction Factors ◽

Immunodeficiency Virus

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Histologic Classification and Immunophenotype of Lymphosarcomas in Cats with Naturally and Experimentally Acquired Feline Immunodeficiency Virus Infections

Veterinary Pathology ◽

10.1177/030098589603300302 ◽

1996 ◽

Vol 33 (3) ◽

pp. 264-272 ◽

Cited By ~ 75

Author(s):

J. J. Callanan ◽

B. A. Jones ◽

J. Irvine ◽

B. J. Willett ◽

I. A. P. McCandlish ◽

...

Keyword(s):

B Cell ◽

Feline Immunodeficiency Virus ◽

Cell Activation ◽

Polyclonal Antibodies ◽

Leukemia Virus ◽

Feline Leukemia Virus ◽

B Cell Activation ◽

Virus Infections ◽

Histologic Classification ◽

Immunodeficiency Virus

Lymphosarcoma (malignant lymphoma) is the commonest hematopoietic tumor in the cat. Many cases are associated with feline leukemia virus (FeLV) infection, but epidemiologic and experimental data suggest that feline immunodeficiency virus (FIV) may also have a role in lymphomagenesis. In this paper, we describe the clinical presentation, histologic classification, and immunophenotype of lymphosarcoma in eight domestic cats with natural or experimental FIV infections. The tumors were often of unusual distribution, with the majority of cases conforming to the least common anatomic classification of “miscellaneous.” Histopathologic and immunophenotypic analysis using a panel of anti-cat and cross-reactive anti-human monoclonal and polyclonal antibodies identified seven of these tumors as high-grade B cell lymphomas of the centroblastic or immunoblastic subtypes. The remaining case was a T-cell tumor associated with a concurrent FeLV infection. Our findings, together with the results of an analysis of FIV proviral DNA in these tumors, indicate that the B-cell lymphosarcomas were comparable to those observed in human and simian immunodeficiency virus infections and that the role of FIV in lymphomagenesis is indirect and related to the potential for malignant transformation during polyclonal B cell activation.

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Prevalences of feline leukaemia virus and feline immunodeficiency virus infections in cats in Sydney

Australian Veterinary Journal ◽

10.1111/j.1751-0813.1997.tb15701.x ◽

1997 ◽

Vol 75 (5) ◽

pp. 323-327 ◽

Cited By ~ 43

Author(s):

R. MALIK ◽

K. KENDALL ◽

J. CRIDLAND ◽

S. COULSTON ◽

AJ STUART ◽

...

Keyword(s):

Feline Immunodeficiency Virus ◽

Virus Infections ◽

Leukaemia Virus ◽

Immunodeficiency Virus ◽

Feline Leukaemia Virus

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Feline immunodeficiency virus dendritic cell infection and transfer

Journal of General Virology ◽

10.1099/vir.0.83068-0 ◽

2008 ◽

Vol 89 (3) ◽

pp. 709-715 ◽

Cited By ~ 4

Author(s):

Wendy S. Sprague ◽

Melissa Robbiani ◽

Paul R. Avery ◽

Kevin P. O'Halloran ◽

Edward A. Hoover

Keyword(s):

T Cells ◽

T Cell ◽

Viral Replication ◽

Feline Immunodeficiency Virus ◽

De Novo ◽

Cell Interactions ◽

Virus Infections ◽

Cell Infection ◽

Immunodeficiency Virus ◽

Viral Transfer

Feline immunodeficiency virus (FIV) interacts with dendritic cells (DC) during initiation of infection, but whether DC support or transfer FIV infection remains unclear. To address this issue, we studied the susceptibility of feline myeloid DC to FIV infection and assessed potential transfer of infection from DC to CD4+ T cells. FIV was detected in membrane-bound vesicles of DC within 2 h of inoculation, although only low concentrations of FIV DNA were found in virus-exposed isolated DC. Addition of resting CD4+ T cells increased viral DNA levels; however, addition of activated CD4+ T cells resulted in a burst of viral replication manifested by FIV p27 capsid antigen generation. To determine whether transfer of FIV infection required productively infected DC (vs virus bound to DC but not internalized), virus-exposed DC were cultured for 2 days to allow for degradation of uninternalized virus and initiation of infection in the DC, then CD4+ T blasts were added. Infection of T cells remained robust, indicating that T-cell infection is likely to be mediated by de novo viral infection of DC followed by viral transfer during normal DC/T-cell interactions. We conclude that feline DC support restricted FIV infection, which nevertheless is sufficient to efficiently transfer infection to susceptible T cells and trigger the major burst of viral replication. Feline DC/FIV/T-cell interactions (similar to those believed to occur in human immunodeficiency virus and simian immunodeficiency virus infections) highlight the means by which immunodeficiency-inducing lentiviruses exploit normal DC/T-cell interactions to transfer and amplify virus infection.

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