Predictors of sense of coherence in typically developing adolescent siblings of individuals with autism spectrum disorder.

BACKGROUND: Children with autism spectrum disorder (ASD) may be a stressor for family members yet there is little published research on the impact of having a child with ASD on their typically developing (TD) adolescent siblings. According to Antonovsky's salutogenic model, a strong sense of coherence leads to the view that the stressor is a manageable challenge rather than a burden and promotes healthier adaptation. This study examines the relationship between stress, TD sibling resources and the sense of coherence in TD siblings. METHOD: This quantitative mail-based study uses a survey methodology, analysing the responses of TD adolescent siblings (n = 96) of individuals with autism, Asperger's syndrome, or pervasive developmental disorder - not otherwise specified to several rating scales. Adolescent siblings, ages 11 to 18 years, completed the Adolescent Coping Orientation for Problem Experience (ACOPE), Network of Relationship Inventory - Social Provision Version (NRI-SPV), Youth Self Report (YSR), and Sense of Coherence (SOC) instruments; parents completed the Child Autism Rating Scale - 2nd Edition (CARS-2). RESULTS: The salutogenesis model was used to guide and inform this research. Findings suggested the following: (a) the stress of ASD severity and resource of adjustment are related in TD adolescent siblings; (b) TD sibling adjustment has a strong relationship with sense of coherence levels; and (c) a greater number of positive coping strategies buffer TD sibling coherence levels when ASD severity scores are high. CONCLUSIONS: ASD severity and TD adolescent sibling resources influence sense of coherence in adolescent TD siblings of individuals with ASD.

Probabilistic Models for Inference about Identity.

Many face recognition algorithms use "distance-based" methods: Feature vectors are extracted from each face and distances in feature space are compared to determine matches. In this paper, we argue for a fundamentally different approach. We consider each image as having been generated from several underlying causes, some of which are due to identity (latent identity variables, or LIVs) and some of which are not. In recognition, we evaluate the probability that two faces have the same underlying identity cause. We make these ideas concrete by developing a series of novel generative models which incorporate both within-individual and between-individual variation. We consider both the linear case, where signal and noise are represented by a subspace, and the nonlinear case, where an arbitrary face manifold can be described and noise is position-dependent. We also develop a "tied" version of the algorithm that allows explicit comparison of faces across quite different viewing conditions. We demonstrate that our model produces results that are comparable to or better than the state of the art for both frontal face recognition and face recognition under varying pose.

Verbal communication outcomes in children with autism after in-home father training.

BACKGROUND: This retrospective study examined the efficacy of in-home father training on the communicative outcomes of children with autism. The in-home training consisted of two components: (1) expectant waiting; and (2) imitation with animation. METHODS: Efficacy of parent training was examined by measuring the ratio of utterances produced by the parents to the utterances produced by the children and the number of verbal imitation by the parents. Outcomes of the children's verbal production were examined by measuring the number of (1) single word utterances; (2) different words produced; and (3) verbal response to questions. RESULTS: Following training there was a decrease in the ratio of parent to child utterances and an increase in (1) the use of imitation by the parents; and (2) the number of single words and different words produced by the children. DISCUSSION: Results of this study suggested that the parents had learned to wait for their children to communicate verbally during communicative interactions and to interact more efficiently with their children by using verbal imitation. Overall, the results of this study support the efficacy of parent training that focuses on promotion of social reciprocity, and have important implications for clinicians and future research.

Inhibition of the ERK pathway prevents HIVgp120-induced REM sleep increase.

Approximately 35% of HIV-infected subjects, both children and adults, exhibit alterations in the sleep-waking cycle. HIV surface glycoprotein gp120 has been postulated to contribute to this abnormality. For example, it has been reported that HIVgp120 modifies sleep in freely-moving rats and that it also activates the ERK pathway in brain slices. The goal of this work was to determine if sleep changes induced by HIVgp120 in normal rats are mediated by the MAPK pathway. Our results show that a single intraventricular administration of HIVgp120 selectively increases REMS and that such an increase can be prevented by U0126, an inhibitor of ERK activating enzyme, MEK. In contrast, SB202190, a MAPK-p38 inhibitor, had no effect on HIVgp120-induced increase in REMS. These results suggest that HIVgp120 increases REMS in the rat by specifically affecting the ERK signal transduction pathway.

Molecular basis for the relative substrate specificity of human immunodeficiency virus type 1 and feline immunodeficiency virus proteases.

We have used a random hexamer phage library to delineate similarities and differences between the substrate specificities of human immunodeficiency virus type 1 (HIV-1) and feline immunodeficiency virus (FIV) proteases (PRs). Peptide sequences were identified that were specifically cleaved by each protease, as well as sequences cleaved equally well by both enzymes. Based on amino acid distinctions within the P3-P3' region of substrates that appeared to correlate with these cleavage specificities, we prepared a series of synthetic peptides within the framework of a peptide sequence cleaved with essentially the same efficiency by both HIV-1 and FIV PRs, Ac-KSGVF/VVNGLVK-NH(2) (arrow denotes cleavage site). We used the resultant peptide set to assess the influence of specific amino acid substitutions on the cleavage characteristics of the two proteases. The findings show that when Asn is substituted for Val at the P2 position, HIV-1 PR cleaves the substrate at a much greater rate than does FIV PR. Likewise, Glu or Gln substituted for Val at the P2' position also yields peptides specifically susceptible to HIV-1 PR. In contrast, when Ser is substituted for Val at P1', FIV PR cleaves the substrate at a much higher rate than does HIV-1 PR. In addition, Asn or Gln at the P1 position, in combination with an appropriate P3 amino acid, Arg, also strongly favors cleavage by FIV PR over HIV PR. Structural analysis identified several protease residues likely to dictate the observed specificity differences. Interestingly, HIV PR Asp30 (Ile-35 in FIV PR), which influences specificity at the S2 and S2' subsites, and HIV-1 PR Pro-81 and Val-82 (Ile-98 and Gln-99 in FIV PR), which influence specificity at the S1 and S1' subsites, are residues which are often involved in development of drug resistance in HIV-1 protease. The peptide substrate KSGVF/VVNGK, cleaved by both PRs, was used as a template for the design of a reduced amide inhibitor, Ac-GSGVF Psi(CH(2)NH)VVNGL-NH(2.) This compound inhibited both FIV and HIV-1 PRs with approximately equal efficiency. These findings establish a molecular basis for distinctions in substrate specificity between human and feline lentivirus PRs and offer a framework for development of efficient broad-based inhibitors.

Viral evolution in response to the broad-based retroviral protease inhibitor TL-3.

TL-3 is a protease inhibitor developed using the feline immunodeficiency virus protease as a model. It has been shown to efficiently inhibit replication of human, simian, and feline immunodeficiency viruses and therefore has broad-based activity. We now demonstrate that TL-3 efficiently inhibits the replication of 6 of 12 isolates with confirmed resistance mutations to known protease inhibitors. To dissect the spectrum of molecular changes in protease and viral properties associated with resistance to TL-3, a panel of chronological in vitro escape variants was generated. We have virologically and biochemically characterized mutants with one (V82A), three (M46I/F53L/V82A), or six (L24I/M46I/F53L/L63P/V77I/V82A) changes in the protease and structurally modeled the protease mutant containing six changes. Virus containing six changes was found to be 17-fold more resistant to TL-3 in cell culture than was wild-type virus but maintained similar in vitro replication kinetics compared to the wild-type virus. Analyses of enzyme activity of protease variants with one, three, and six changes indicated that these enzymes, compared to wild-type protease, retained 40, 47, and 61% activity, respectively. These results suggest that deficient protease enzymatic activity is sufficient for function, and the observed protease restoration might imply a selective advantage, at least in vitro, for increased protease activity.

Structure-activity studies of FIV and HIV protease inhibitors containing allophenylnorstatine.

The interaction of P1 and P3 side chains with the combining S1 and S3 hydrophobic subsites of HIV and FIV proteases has been explored using asymmetric competitive inhibitors. The inhibitors evaluated contained (2S,3S)-3-amino-2-hydroxy-4-phenylbutyric acid (allophenylnorstatine) as the hydroxymethylcarbonyl isostere, (R)-5,5-dimethyl-1, 3-thiazolidine-4-carbonyl as P1', Val as P2 and P2' residues, and a variety of amino acids at the P3 and P3' positions. All inhibitors showed competitive inhibition of both enzymes with higher potency against the HIV protease in vitro. Within this series, 31 (VLE776) is the most effective inhibitor against FIV protease, and it contains Phe at P3, but no P3' residue. VLE776 also exhibited potent antiviral activities against the drug-resistant HIV mutants (G48V and V82F) and the TL3-resistant HIV mutants. Explanation of the inhibition activities was described. In addition, a new strategy was described for development of bifunctional inhibitors, which combine the protease inhibitor and another enzyme inhibitor in one molecule.

Binding of recombinant feline immunodeficiency virus surface glycoprotein to feline cells: role of CXCR4, cell-surface heparans, and an unidentified non-CXCR4 receptor.

To address the role of CXCR4 in the cell-surface attachment of the feline immunodeficency virus (FIV), a soluble fusion protein, gp95-Fc, consisting of the surface glycoprotein (SU, gp95) of either a primary (PPR) or cell line-adapted (34TF10) FIV strain was fused in frame with the Fc domain of human immunoglobulin G1. The recombinant SU-immunoadhesins were used as probes to investigate the cellular binding of FIV SU. In agreement with the host cell range properties of both viruses, binding of 34TF10 gp95-Fc was observed for all cell lines tested, whereas PPR gp95-Fc bound only to primary feline T cells. 34TF10 gp95-Fc also bound to Jurkat and HeLa cells, consistent with the ability of FIV to use human CXCR4 as a fusion receptor. As expected, 34TF10 gp95-Fc binding to Jurkat cells was blocked by addition of stromal cell-derived factor 1alpha (SDF-1alpha), as was binding to the 3201 feline lymphoma cell line. However, SDF-1alpha, RANTES, macrophage inflammatory protein 1beta, and heparin all failed to inhibit the binding of either gp95-Fc to primary T cells, suggesting that a non-CXCR4 receptor is involved in the binding of FIV SU. In this regard, an unidentified 40-kDa protein species from the surface of primary T cells but not Jurkat and 3201 cells specifically coprecipitated with both gp95-Fc. Yet another type of binding of 34TF10 gp95-Fc to adherent kidney cells was noted. SDF-1alpha failed to block the binding of 34TF10 gp95-Fc to either HeLa, Crandel feline leukemia, or G355-5 cells. However, binding was severely impaired in the presence of soluble heparin, as well as after enzymatic removal of surface heparans or on cells deficient in heparan expression. These overall findings suggest that in addition to CXCR4, a non-CXCR4 receptor and cell-surface heparans also play an important role in FIV gp95 cell surface interactions on specific target cells.

Design, synthesis, and biological evaluation of HIV/FIV protease inhibitors incorporating a conformationally constrained macrocycle with a small P3' residue.

A series of norstatine-based HIV/FIV protease inhibitors incorporating a 15-membered macrocycle as a mimic of the tripeptide (Ala-Val-Phe), a motif with a small P3' residue elective against the FIV protease and the drug-resistant HIV proteases, has been synthesized. It was found that the macrocycle is important to the overall activity of the inhibitors. Certain inhibitors were developed expressing low nanomolar inhibitory activity against the HIV/FIV proteases and they are also effective against some drug-resistant as well as TL3-resistant HIV proteases.

A follow-up study of beliefs held by parents of children with pervasive developmental delay.

PROBLEM: Little is known about the effects of parental beliefs on children with disorders such as pervasive developmental delay (PDD). METHODS: A six-question, semistructured, videotaped interview was used to gather preliminary descriptive data from 44 caregivers regarding beliefs about their PDD children (ages 3-15 years). Children and caregivers were selected by purposive sampling from a preadmission waiting list for a child psychiatric inpatient unit. FINDINGS: While responses varied, most caregivers shared concerns about delayed child development, appropriateness of school placement, and future planning. In addition, some indicated they possess inaccurate beliefs regarding the intention of child behavior as well as the PDD diagnosis. All indicated a need for direction in how to effectively help the children. CONCLUSIONS: Parental responses to the interview questions support the author's clinical observations regarding the need for nurse-conducted parent training programs. Parent training should focus on correcting inaccurate parental beliefs and teaching effective ways to promote child development and manage maladaptive behaviors.

The role of retroviral dUTPases in replication and virulence.

Several retroviruses, including equine infectious anemia virus (EIAV), visna virus, caprine arthritis-encephalitis virus (CAEV) and feline immunodeficiency virus (FIV) encode dUTPase. The role of this enzyme in the replication of these viruses has been scrutinized, with particular emphasis on potential roles for dUTPase in virulence and viral mutation rate. Overall, the results of these studies have indicated a central role for dUTPase in facilitating productive viral replication in non-dividing cells. The requirement for dUTPase in EIAV, which replicates exclusively in macrophages, may be the most stringent. Studies of dUTPase mutants of virulent EIAV clones suggest that the enzyme is a major determinant of virulence. In contrast, FIV readily replicates in dividing cell populations such as CD4+ and CD8+ T cells, and B cells as well as in non-dividing macrophages. Thus, the virus burden and disease sequelae are lowered in cats infected with a dUTPase-minus FIV relative to cats infected with wild type FIV, but not totally abrogated. Growth in macrophages is attenuated with the DU-minus FIV with evidence of a 5 to 8-fold increase in G-->A transition mutations in viral integrants present in macrophages. These findings are consistent with an increase in uracil misincorporation in the absence of dUTPase, resulting in transition mutations that cripple the virus. Effects on virus replication and disease production have also been noted for dUTPase-deleted CEAV and visna virus. While HIV and SIV do not encode dUTPase some reports suggest that other viral and host cell factors may substitute for its activity. Betaretroviruses also encode dUTPase and while several of these cause significant disease, the role of dUTPase in their replication and pathogenesis is currently unknown.

The effects of blur and size on monocular and stereoscopic localization.

Monocular localization of non-abutting stimuli and stereoscopic localization of the same second-order targets are performed with the same precision (Wilcox, L.M. & Hess, R.F. (1996) Is the site of non-linear filtering in stereopsis before or after binocular combination? Vision Research, 36, 391-399). Further, both tasks show a similar dependence on the scale of the stimulus. Since prior studies used Gaussian-enveloped stimuli, modifications of stimulus scale produced concurrent changes in edge blur. The experiments reported here assess the relative contributions of size and blur to the observed dependence on envelope scale for both monocular localization and stereoacuity. Stereoacuity for first-order targets was found to be an order of magnitude better than stereoacuity for second-order targets and monocular acuity for both first- and second-order targets. Further, while first-order stereopsis was found to depend solely on blur, second-order stereoacuity and monocular acuity were affected by both size and blur. These results suggest that while stereoacuity for first-order stimuli may be determined by a correlative process limited by early additive noise, stereoacuity for second-order stimuli and monocular acuity for non-abutting targets are more likely limited by stimulus-dependent spatial subsampling.

Developmental Stifling: an emerging symptom pattern.

"Developmental Stifling" is a term recently developed by us to denote a symptom pattern observed in a variety of clinical practice sites. The purpose of our paper is to define developmental stifling and compare this recently identified condition with Munchausen Syndrome by Proxy. A case example of developmental stifling is provided, as well as recommendations for early identification and treatment.

Identification of efficiently cleaved substrates for HIV-1 protease using a phage display library and use in inhibitor development.

The recognition sequences for substrate cleavage by aspartic protease of HIV-1 are diverse and cleavage specificities are controlled by complex interactions between at least six amino acids around the cleavage site. We have identified 45 efficiently cleaved peptide substrates of HIV-1 protease (PR) using substrate phage display, an approach that can elucidate both context-dependent and context-independent preferences at individual subsites of a protease substrate. Many of the selected peptides were cleaved more efficiently and had lower K(m) values than physiologically relevant substrates of HIV-1 PR. Therefore, mutations occurring in the cleavage sites of the Gag and Gag-pol polyproteins of HIV-1 could significantly lower the K(m) values to better compete against drugs for protease binding while maintaining cleavage rates necessary for viral replication. The most efficiently cleaved peptide substrate derived from these phage, Ac-GSGIF*LETSL-NH(2), was cleaved 60 times more efficiently and had a K(m) approximately 260 times lower than a nine-amino-acid peptide based on the natural reverse transcriptase/integrase cleavage site when assayed at pH 5.6, 0.2 M NaCl. The peptide substrates selected served as frameworks for synthesis of tight binding reduced amide inhibitors of HIV-1 PR. The results show that the most efficiently cleaved substrates serve as the best templates for synthesis of the tightest binding inhibitors. Thus, defining changes in substrate preferences for drug-resistant proteases may aid in the development of more efficacious inhibitors.

Structures of feline immunodeficiency virus dUTP pyrophosphatase and its nucleotide complexes in three crystal forms.

dUTP pyrophosphatase (dUTPase) cleaves the alpha-beta phosphodiester of dUTP to form pyrophosphate and dUMP, preventing incorporation of uracil into DNA and providing the substrate for thymine synthesis. Seven crystal structures of feline immunodeficiency virus (FIV) dUTPase in three crystal forms have been determined, including complexes with substrate (dUTP), product (dUMP) or inhibitor (dUDP) bound. The native enzyme has been refined at 1.40 A resolution in a hexagonal crystal form and at 2.3 A resolution in an orthorhombic crystal form. In the dUDP complex in a cubic crystal form refined at 2.5 A resolution, the C-terminal conserved P-loop motif is fully ordered. The analysis defines the roles of five sequence motifs in interaction with uracil, deoxyribose and the alpha-, beta- and gamma-phosphates. The enzyme utilizes adaptive recognition to bind the alpha- and beta-phosphates. In particular, the alpha-beta phosphodiester adopts an unfavorable eclipsed conformation in the presence of the P-loop. This conformation may be relevant to the mechanism of alpha-beta phosphodiester bond cleavage.

HIV- and FIV-derived gp120 alter spatial memory, LTP, and sleep in rats.

Human immunodeficiency virus (HIV)-associated dementia (HAD) has been detected in 20-30% of patients suffering AIDS. The envelope glycoprotein 120 (gp120) derived from HIV seems to play a critical role in the pathophysiology of this dementia. Likewise, the feline immunodeficiency virus (FIV)-derived gp120 causes neurological and electrophysiological abnormalitites in cats. We have studied the effects of gp120 derived from HIV or FIV on learning and memory processing, hippocampal long-term potentiation (LTP), hippocampal neuronal cAMP production, the sleep-waking cycle, and locomotor activity and equilibrium in rats. Results showed that while both HIV- and FIV-gp120 impaired the rat's performance in the Barnes maze task, only HIVgp120 impaired the induction and maintenance of LTP. However, both glycoproteins induced a significant decrease in the posttetanic potentiation. HIVgp120 also caused a significant reduction in cAMP production in the hippocampus. Regarding the sleep-waking cycle, HIV- and FIV-gp120 increased the waking state and slow-wave sleep 1 (SWS1), while decreasing both SWS2 and REM sleep. Locomotor activity and equilibrium were significantly altered by these glycoproteins. These results suggest that HIVgp120 causes neurophysiological abnormalities and therefore may facilitate HAD development in AIDS patients.

HIV-derived protein gp120 suppresses P3 potential in rats: potential implications in HIV-associated dementia.

Between 20 and 30% of AIDS patients have neurological symptoms characterized by motor impairment, memory loss and progressive dementia. Previous studies have implicated the HIV derived gp120, which produces behavioral deficits and electrophysiological alterations in rats. The goal of the present study was to describe the effect of this protein on the P3 event-related potential (ERP), evoked by a passive discrimination task in rats. We used II rats divided into two groups: HIV gp120 (n = 6) and control (n = 5). We recorded the P3 wave before any treatment (baseline), during the i.c.v. administration of either HIVgp 120 (700 ng/5 days) or saline (pH 7.2), and 24 h, 7, 14 and 21 days after the last injection. There were no changes between groups in the amplitude or latencies of the observed components (N1, P2, N2 and P3) evoked by target stimuli, during baseline or during the injection period. However, the HIV gp120 group showed a significant amplitude reduction in P3 wave 24 h after the last injection, while the N1, P2 and N2 waves remained unchanged. However, from the 7th day through the 21st day, P2 and N2 components also disappeared and only the N1 component could be observed in the HIV gp 20-treated group. These changes in the N2, P2 and P3 potentials, suggesting an alteration in cognitive processes, further support the neurotoxic activity of HIV gp120 and its role in AIDS dementia.

Multiple antiviral activities of cyanovirin-N: blocking of human immunodeficiency virus type 1 gp120 interaction with CD4 and coreceptor and inhibition of diverse enveloped viruses.

Cyanovirin-N (CV-N) is a cyanobacterial protein with potent neutralizing activity against human immunodeficiency virus (HIV). CV-N has been shown to bind HIV type 1 (HIV-1) gp120 with high affinity; moreover, it blocks the envelope glycoprotein-mediated membrane fusion reaction associated with HIV-1 entry. However, the inhibitory mechanism(s) remains unclear. In this study, we show that CV-N blocked binding of gp120 to cell-associated CD4. Consistent with this, pretreatment of gp120 with CV-N inhibited soluble CD4 (sCD4)-dependent binding of gp120 to cell-associated CCR5. To investigate possible effects of CV-N at post-CD4 binding steps, we used an assay that measures sCD4 activation of the HIV-1 envelope glycoprotein for fusion with CCR5-expressing cells. CV-N displayed equivalently potent inhibitory effects when added before or after sCD4 activation, suggesting that CV-N also has blocking action at the level of gp120 interaction with coreceptor. This effect was shown not to be due to CV-N-induced coreceptor down-modulation after the CD4 binding step. The multiple activities against the HIV-1 envelope glycoprotein prompted us to examine other enveloped viruses. CV-N potently blocked infection by feline immunodeficiency virus, which utilizes the chemokine receptor CXCR4 as an entry receptor but is CD4 independent. CV-N also inhibited fusion and/or infection by human herpesvirus 6 and measles virus but not by vaccinia virus. Thus, CV-N has broad-spectrum antiviral activity, both for multiple steps in the HIV entry mechanism and for diverse enveloped viruses. This broad specificity has implications for potential clinical utility of CV-N.

Alteration of substrate and inhibitor specificity of feline immunodeficiency virus protease.

Feline immunodeficiency virus (FIV) protease is structurally very similar to human immunodeficiency virus (HIV) protease but exhibits distinct substrate and inhibitor specificities. We performed mutagenesis of subsite residues of FIV protease in order to define interactions that dictate this specificity. The I37V, N55M, M56I, V59I, and Q99V mutants yielded full activity. The I37V, N55M, V59I, and Q99V mutants showed a significant increase in activity against the HIV-1 reverse transcriptase/integrase and P2/nucleocapsid junction peptides compared with wild-type (wt) FIV protease. The I37V, V59I, and Q99V mutants also showed an increase in activity against two rapidly cleaved peptides selected by cleavage of a phage display library with HIV-1 protease. Mutations at Q54K, I98P, and L101I dramatically reduced activity. Mutants containing a I35D or I57G substitution showed no activity against either FIV or HIV substrates. FIV proteases all failed to cut HIV-1 matrix/capsid, P1/P6, P6/protease, and protease/reverse transcriptase junctions, indicating that none of the substitutions were sufficient to change the specificity completely. The I37V, N55M, M56I, V59I, and Q99V mutants, compared with wt FIV protease, all showed inhibitor specificity more similar to that of HIV-1 protease. The data also suggest that FIV protease prefers a hydrophobic P2/P2' residue like Val over Asn or Glu, which are utilized by HIV-1 protease, and that S2/S2' might play a critical role in distinguishing FIV and HIV-1 protease by specificity. The findings extend our observations regarding the interactions involved in substrate binding and aid in the development of broad-based inhibitors.

Feline immunodeficiency virus Vif localizes to the nucleus.

Monoclonal antibodies prepared against recombinant Vif derived from the 34TF10 strain of feline immunodeficiency virus (FIV) were used to assess the expression and localization of Vif in virus-infected cells. Analyses by Western blotting and by immunoprecipitation from cells infected with FIV-34TF10 revealed the presence of a single 29-kDa species specific for virus-infected cells. Confirmation of antibody specificity was also performed by specific immunoprecipitation of in vitro-transcribed and -translated recombinant Vif. Localization experiments were also performed on virus-infected cells, using different fixation procedures. Results for methanol fixation protocols similar to those reported for localization of human immunodeficiency virus (HIV) Vif showed a predominant cytoplasmic localization for FIV Vif, very similar to localization of HIV type 1 Vif and virtually identical to the localization observed for the Gag antigens of the virus. However, with milder fixation procedures that used 2% formaldehyde at 4 degrees C, FIV Vif was strongly evident in the nucleus. The localization was distinct from the nuclear localization noted with Rev and did not involve the nucleolus. Attempts to show colocalization or coprecipitation of Vif with Gag antigens were unsuccessful. In addition, Vif was not detected in purified FIV virions. The results are consistent with the notion that the primary role of Vif in virus infection initiates in the nucleus.