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At least 19 recordsLinked to original sources

PubMed2025

Predicting host tropism in influenza a viruses: insights from multi-segment nucleotide signatures.

BACKGROUND: Influenza A virus (IAV) poses a significant public health threat due to its cross-species transmission and complex host adaptation mechanisms. This study integrated whole-genome data from avian, human, swine, and bovine IAV strains, using machine learning to predict viral host tropism based on nucleotide site features and to identify key sites driving host adaptation along with their synergistic effects. METHODS: A total of 64,000 IAV sequences from avian, human, swine, and bovine hosts were analyzed to build host-prediction models. A four-class classification framework (avian, human, swine, bovine) was constructed using nucleotide site features from all eight genomic segments (PB2, PB1, PA, HA, NP, NA, MP, NS). Eight machine learning algorithms (logistic regression, decision tree, random forest, SVM, KNN, gradient boosting, XGBoost, LightGBM) were benchmarked via 10-fold stratified cross-validation. Model performance was evaluated using accuracy, precision, recall, F1-score, AUPRC, and AUC. SHAP (SHapley Additive exPlanations) analysis prioritized critical nucleotide sites, while bivariate association tests identified synergistic/antagonistic interactions between sites. Nucleotide composition profiles were compared across host groups using hierarchical clustering and heatmap visualization. RESULTS: The XGBoost algorithm demonstrated the best and most stable performance, achieving an AUC value of over 0.95 in distinguishing human-derived sequences from non-human ones. SHAP analysis identified the top 20 critical nucleotide sites for each gene segment, such as sites 46 and 698 in the NS segment. Nucleotide composition analysis revealed high similarity between human and swine sequences in the HA and PB2 segments, and between avian and bovine sequences. The HA segment was particularly challenging in differentiating human from swine strains. Bivariate site association analysis uncovered significant synergistic or antagonistic effects between key sites within gene segments, forming complex networks. For instance, in the NS segment, a positive prediction contribution was observed when sites 371, 698, and 419 were all G. CONCLUSIONS: This study advances our mechanistic understanding of IAV host adaptation, identifies molecular determinants for zoonotic risk stratification, and establishes a scalable machine learning framework for predicting viral host tropism through nucleotide signature analysis, thereby enhancing surveillance strategies and informing preventive measures against emerging viral threats.

Influenza A virus↗

PubMed2026

Lineage-associated differences in adenine methylation patterns of mammalian-associated Campylobacter fetus isolates: a possible role for epigenetic factors in host tropism and pathogenesis.

Mammalian Campylobacter fetus (CF) is divided into two subspecies, C. fetus fetus (CFF) and C. fetus venerealis (CFV), the latter being bovine-adapted and responsible for the notifiable disease bovine genital campylobacteriosis (BGC). Differentiation between CF subspecies has traditionally been undertaken by a few biochemical tests, but these are complicated by the existence of a biotype, C. fetus venerealis intermedius (CFVi), which shares attributes of both CFF and CFV. Molecular methods targeting specific genes have gained acceptance for more accurate subtype identification and align well with whole-genome analysis. However, limited genomic diversity between subtypes has confounded efforts to understand the genetic basis for differential host tropism and pathogenesis of these organisms. A previous study of a small cohort of C. fetus isolates suggested that dam gene coding variations might correlate with CF subtype. Accordingly, this study examines a cohort of 331 C. fetus genomes, representative of all seven phylogenetic groups for their complement of adenine methylases and the genomic motifs they target in representative isolates. All CF isolates retained a cfeM1 gene, the presence of which correlates with RAATTY methylation, while seven other adenine methylase genes exhibited distinct cladal distributions. Notably, a cjeM1 gene appears to target the CCAN7TAG/CTAN7TGG motif in CFV and CFVi isolates only. Given the increasing recognition of the impact of adenine methylation on bacterial-host interactions, further exploration of the role of adenine methylation in C. fetus pathogenesis could reveal mechanisms contributing to BGC and thus aid in its eradication.IMPORTANCECampylobacter fetus remains an important zoonotic pathogen, for which a better understanding of its host tropism and pathogenesis is sought. However, the limited genomic variation observed between subtypes has to date confounded efforts in this regard. This study suggests that an alternative approach that examines epigenetic differences between subtypes, specifically adenine methylation patterns, may reveal mechanisms critical to the pathologies of these organisms.

Animals↗

PubMed1976

Selective adherence as a determinant of the host tropisms of certain indigenous and pathogenic bacteria.

The relationship between the selective abilities of bacteria to adhere and their predilections for colonizing different mammalian hosts was investigated by using bacteria indigenous to the tongue dorsum of humans and rats as models. Streptococcus salivarius and S. sanguis averaged 22.6 and 2.8%, respectively, of the cultivable bacteria recovered from swab samples of the tonges of five humans, but these organisms were not indigenous on the tongues of rats (Charles River strain). S. faecalis and serum-requiring diphtheroids were consistently prominant on the tongues of rats, but they were not detected on the tongues of the humans examined. The ability of these organisms to adhere to the tongue surface of the hosts was compared by introducing mixtures of streptomycin-resistant strains into the mouths of human volunteers and rats. S. salivarius adhered in higher proportions to the dorsal tongue surface of humans than did strains of S. faecalis and the serum-requiring diphtheroid. S. sanguis also adhered to human tongues better than the serum-requiring diphtheroid. However, S. faecalis and the serum-requiring diphtheroid sorbed in higher proportions to the tongues of rats. In an in vivo assay, human strains of S. pyogenes and S. salivarius attached in higher numbers to buccal epithelial cells derived from humans than to those obtained from rats, whereas the reverse was observed with a serum-requiring diphtheroid derived from rats. Collectively, these studies show that bacteria sorb with a high degree of specificity to the tissues of different mammalian hosts, and the relative adherence of the organisms studied correlated with their natural host tropisms. The selective adherence of S. salvarius and S. faecalis was similar to the tongues of conventional and germ-free rats, suggesting that the presence of an indigenous bacterial flora did not significantly influence their attachment selectivity. Moreover, the ability of these organisms to colonize the tongues of gnotobiotic rats lacking an indigenous flora paralleled their adherence selectivity. Direct scanning microscopic observations indicated that the tongue dorsum of conventional rats is highly papillated but contains relatively sparse bacterial populations. Indigenous organisms colonized the bases of papillae on the anterior tip and lateral edges of the tongue as discrete microcolonies, but bacteria were rarely observed on other papillae. This localized and restricted pattern of colonization and the spatial distribution of the microcolonies of indigenous bacteria present also suggest that antagonistic interactions are unlikely to account for the bacterial tropisms observed for colonization of the tongues of rats.

Animals↗

PubMed2007

Avian hepatitis B viruses: molecular and cellular biology, phylogenesis, and host tropism.

The human hepatitis B virus (HBV) and the duck hepatitis B virus (DHBV) share several fundamental features. Both viruses have a partially double-stranded DNA genome that is replicated via a RNA intermediate and the coding open reading frames (ORFs) overlap extensively. In addition, the genomic and structural organization, as well as replication and biological characteristics, are very similar in both viruses. Most of the key features of hepadnaviral infection were first discovered in the DHBV model system and subsequently confirmed for HBV. There are, however, several differences between human HBV and DHBV. This review will focus on the molecular and cellular biology, evolution, and host adaptation of the avian hepatitis B viruses with particular emphasis on DHBV as a model system.

Amino Acid Sequence↗

PubMed1983

Physical mapping of the Fv-1 tropism host range determinant of BALB/c murine leukemia viruses.

The murine leukemia viruses (MuLVs) have different host ranges and were originally designated N-tropic and B-tropic if they replicated preferentially in vitro on NIH and BALB/c fibroblasts, respectively. It was later found that N-tropic MuLVs were in fact restricted in BALB/c cells, that B-tropic MuLVs were restricted in NIH cells, and that both viruses were restricted in (BALB X NIH) F1 cells. A single gene, Fv-1, with two alleles, Fv-1b and Fv-1n, determines this dominant restriction. A virus-encoded protein seems to carry the viral host range determinant which is recognized by the Fv-1 gene product. To map the viral DNA sequences encoding this determinant, we constructed viral DNA recombinants in vitro between the cloned infectious viral DNA genomes from BALB/c N-tropic and B-tropic MuLVs. Infectious recombinant MuLVs were recovered by microinjecting these recombinant DNAs into murine Fv-1- SC-1 cells and were subsequently tested in vitro for their host ranges (N- or B-tropic). We found that a short 302-base pair 5'-end fragment was necessary and sufficient to confer a specific host range to a recombinant. Our sequencing data revealed that this fragment codes for amino acid sequences in gag p30. They also showed that only two consecutive amino acid differences, Gln-ArgN- and Thr-GluB-, in p30 are responsible for the N- and B-tropic host ranges of the BALB/c MuLVs, respectively. Therefore, it appears that the Fv-1b and Fv-1n gene products can discriminate between these two p30 amino acid sequences.

Amino Acid Sequence↗

PubMed2005

Chlamydial IFN-gamma immune evasion is linked to host infection tropism.

Chlamydiae are obligate intracellular pathogens that can exhibit a broad host range in infection tropism despite maintaining near genomic identity. Here, we have investigated the molecular basis for this unique host-pathogen relationship. We show that human and murine chlamydial infection tropism is linked to unique host and pathogen genes that have coevolved in response to host immunity. This intimate host-pathogen niche revolves around a restricted repertoire of host species-specific IFN-gamma-mediated effector responses and chlamydial virulence factors capable of inhibiting these effector mechanisms. In human epithelial cells, IFN-gamma induces indoleamine 2,3-dioxygenase expression that inhibits chlamydial growth by depleting host tryptophan pools. Human chlamydial strains, but not the mouse strain, avoid this response by the production of tryptophan synthase that rescues them from tryptophan starvation. Conversely, in murine epithelial cells IFN-gamma induces expression of p47 GTPases, but not indoleamine 2,3-dioxygenase. One of these p47 GTPases (Iigp1) was shown by small interfering RNA silencing experiments to specifically inhibit human strains, but not the mouse strain. Like human strains and their host cells, the murine strain has coevolved with its murine host by producing a large toxin possessing YopT homology, possibly to circumvent host GTPases. Collectively, our findings show chlamydial host infection tropism is determined by IFN-gamma-mediated immunity.

Animals↗

PubMed2000

Role for a secreted cysteine proteinase in the establishment of host tissue tropism by group A streptococci.

Primary infection of the human host by group A streptococci (GAS) most often involves either the epidermis of the skin or the oropharyngeal mucosa. A humanized in vivo model for impetigo was used to investigate the basis for host tissue tropism among GAS. Disruption of the speB gene (encoding for a secreted cysteine proteinase) led to a loss of virulence for two impetigo-derived strains (M-types 33 and 53), as evidenced by a diminution in tissue damage and a lack of reproductive growth. The level of cysteine proteinase activity in overnight cultures was associated with the extent of gross pathological changes induced by strains displaying varied degrees of virulence in the impetigo model. Moreover, high levels of secreted cysteine proteinase activity correlated with a genetic marker for preferred tissue site of infection at the skin (emm pattern D). The addition of exogenous SpeB to a speB mutant (emm pattern D) or to an avirulent throat-like strain (emm pattern A) led to increased bacterial reproduction at the skin. The data provide both experimental and epidemiological evidence for a critical role of a secreted bacterial protease in promoting host tissue-specific infection.

Bacterial Proteins↗

PubMed2001

Site-directed mutagenesis of intimin alpha modulates intimin-mediated tissue tropism and host specificity.

The hallmark of enteropathogenic (EPEC) and enterohaemorrhagic (EHEC) Escherchia coli adhesion to host cells is intimate attachment leading to the formation of distinctive 'attaching and effacing' lesions. This event is mediated, in part, by binding of the bacterial adhesion molecule intimin to a second bacterial protein, Tir, delivered by a type III secretion system into the host cell plasma membrane. The receptor-binding activity of intimin is localized to the C-terminal 280 amino acids (Int280) and at least five distinct intimin types (alpha, beta, gamma, delta and epsilon) have been identified thus far. In addition to binding to Tir, intimin can also bind to a component encoded by the host. The consequence of latter intimin-binding activity may determine tissue tropism and host specificity. In this study we selected three amino acids in intimin, which are implicated in Tir binding, for site-directed mutagenesis. We used the yeast two-hybrid system and gel overlays to study intimin-Tir protein interaction. In addition, the biological consequences of the mutagenesis was tested using a number of infection models (cultured epithelial cells, human intestinal explants and a mouse model). We report that while an I237/897A substitution (positions numbered according to Int280alpha/whole intimin alpha) in intimin alpha did not have any affect on its biological activity, a T255/914A substitution attenuated intimin activity in vivo. In contrast, the mutation V252/911A affected tissue targeting in the human intestinal explant model and attenuated the biological activity of intimin in the mouse model. This study provides the first clues of the molecular basis of how intimin mediates tissue tropism and host specificity.

Adhesins, Bacterial↗

PubMed2004

Expansion of host-cell tropism of foot-and-mouth disease virus despite replication in a constant environment.

Foot-and-mouth disease virus (FMDV) variants adapted to BHK-21 cells showed an expanded host-cell tropism that extended to primate and human cell lines. Virus replication in human HeLa and Jurkat cells has been documented by titration of virus infectivity, quantification of virus RNA, expression of a virus-specific non-structural antigen, and serial passage of virus in the cells. Parallel serial infections of human Jurkat cells with the same variant FMDVs indicates a strong stochastic component in the progression of infection. Chimeric viruses identified the capsid as a genomic region involved in tropism expansion. These results indicate that, contrary to theoretical predictions, replication of an RNA virus in a constant cellular environment may lead to expansion of cellular tropism, rather than to a more specialized infection of the cellular type to which the virus has been adapted.

Adaptation, Physiological↗

PubMed2004

Host cell tropism underlies species restriction of human and bovine Cryptosporidium parvum genotypes.

It has been recognized recently that human cryptosporidiosis is usually caused by Cryptosporidium parvum genotype I ("human" C. parvum), which is not found in animals. Compared to C. parvum genotype II, little is known of the biology of invasion of the human-restricted C. parvum genotype I. The aims of the present study were (i) to explore and compare with genotype II the pathogenesis of C. parvum genotype I infection by using an established in vitro model of infection and (ii) to examine the possibility that host-specific cell tropism determines species restriction among C. parvum genotypes by using a novel ex vivo small intestinal primary cell model of infection. Oocysts of C. parvum genotypes I and II were used to infect HCT-8 cells and primary intestinal epithelial cells in vitro. Primary cells were harvested from human endoscopic small-bowel biopsies and from bovine duodenum postmortem. C. parvum genotype I infected HCT-8 cells with lower efficiency than C. parvum genotype II. Actin colocalization at the host parasite interface and reduction in levels of invasion after treatment with microfilament inhibitors (cytochalasin B and cytochalasin D) were observed for both genotypes. C. parvum genotype II invaded primary intestinal epithelial cells, regardless of the species of origin. In contrast, C. parvum genotype I invaded only human small-bowel cells. The pathogenesis of C. parvum genotype I differs from C. parvum genotype II. C parvum genotype I does not enter primary bovine intestinal cells, suggesting that the species restriction of this genotype is due to host tissue tropism of the infecting isolate.

Actins↗

PubMed2006

Host cell tropism of equine herpesviruses: glycoprotein D of EHV-1 enables EHV-4 to infect a non-permissive cell line.

Equine herpesviruses 1 and 4 (EHV-1 and EHV-4) cause equine respiratory disease worldwide. However, only EHV-1 is a cause of abortion and neurological disease, despite the two viruses having all 76 genes in common. In addition EHV-1 has a broader host range in cell culture than EHV-4, as exemplified by the rabbit kidney (RK) cell line that is permissive for EHV-1, but not for EHV-4. Here we describe that when EHV-4 produced in equine cells was inoculated onto RK cells expressing glycoprotein D of EHV-1 (RKgD1), infection developed as clusters of rounded cells, and this infectivity could be passaged in RKgD1 cells. The progeny virus could also infect single RK cells, consistent with EHV-4 acquiring EHV1 gD from the complementing cell line. No such infection was observed for EHV-4 in RK cells expressing EHV-1 glycoprotein C. The results are consistent with gD homologues being major determinants of host cell tropism and raise the possibility that gD may be a factor in the differential pathogenicity of EHV-1 and EHV-4.

Animals↗

PubMed1994

Virulence and pathogenesis of non-virulent and virulent strains of pseudorabies virus expressing envelope glycoprotein E1 of hog cholera virus.

Pseudorabies virus (PRV) expressing the envelope glycoprotein E1 (E1) of hog cholera virus (HCV) was used as a model to study the potential risks connected with the use of a live herpesvirus vaccine expressing a foreign gene. The gene encoding E1 was inserted into the glycoprotein X (gX) locus of both a virulent PRV strain and a non-virulent PRV strain in which the virulence genes encoding glycoprotein I (gI) and thymidine kinase (TK) had been inactivated. We investigated whether strain M205 (gI-, TK-, gX-, E1+) had a changed cell or host tropism or virulence compared with strain M206 (gI-, TK-, gX-) in pigs, rabbits, hamsters, rats, mice and rhesus monkeys. The insertion of E1 into this non-virulent PRV strain caused no change in cell or host tropism. However, pigs inoculated with M205 shed less virus over a shorter period than pigs inoculated with M206. Theoretically, virulent PRV strains expressing E1 (gX-, E1+) could arise through transfer of the E1 gene of M205 to a virulent PRV strain. Therefore, we inoculated pigs with strain M12 (gX-, E1+) or the control strain M104 (gX-) and compared the virulence and pathogenesis. M12 and M104 were of approximately equal virulence and the pathogenesis of both strains was similar. We concluded that incorporating E1 of HCV into the gX locus of PRV did not change cell or host tropism, nor did it change the virulence of either non-virulent or virulent PRV.

Animals↗

PubMed1989

Change in host cell tropism associated with in vitro replication of equine infectious anemia virus.

Similar to other human and animal lentiviruses, equine infectious anemia virus (EIAV) is detectable in vivo in cells of the monocyte-macrophage lineage. Owing to their short-lived nature, horse peripheral blood macrophage cultures (HMC) are rarely used for in vitro propagation of EIAV, and equine dermal (ED) or kidney cell cultures, which can be repeatedly passed in vitro, are used in most studies. However, wild-type isolates of EIAV will not grow in these cell types without extensive adaptation, a process which may attenuate viral virulence. To better define the effect of host cell tropism on the virulence and pathogenesis of EIAV, we studied a field isolate of EIAV during in vitro adaptation to growth in an ED cell line. Interestingly, as the virus adapted to growth in ED cells, there was a corresponding decrease in infectivity for HMC, and the final ED-adapted isolate was more than 100-fold more infectious for ED cells than for HMC. In vivo studies indicated that the ED-adapted isolate was able to replicate in experimentally infected horses, although no clinical signs of EIA were observed. Thus, selection for in vitro replication on ED cells correlated with a loss of EIAV tropism for HMC in vitro and was associated with avirulence in vivo.

Animals↗

PubMed2005

Alteration in host cell tropism limits the efficacy of immunization with a surface protein of malaria merozoites.

Immunization with Plasmodium yoelii merozoite surface protein-8 (PyMSP-8) has been shown to protect mice against lethal P. yoelii 17XL malaria. Here we demonstrate that PyMSP-8-specific antibodies preferentially suppress P. yoelii 17XL growth in mature erythrocytes compared to growth in reticulocytes and do not suppress the growth of nonlethal P. yoelii 17X, a parasite that primarily replicates in reticulocytes. The protection against normocyte-associated P. yoelii malaria parasites is mediated by antibodies that recognize conformational epitopes of PyMSP-8 that are nonpolymorphic. We examined changes in gene expression in reticulocyte-restricted P. yoelii 17XL parasites that escaped neutralization by PyMSP-8-specific antibodies using P. yoelii DNA microarrays. Of interest, Pymsp-8 gene expression decreased, while the expression of msp-1, msp-7, and several rhoptry protein genes increased. Breakthrough parasites also exhibited increases in the expression of a subset of yir and Pyst-a genes that are predicted to encode polymorphic antigens expressed on the surface of infected erythrocytes. These data suggest that changes in the expression of parasite proteins expressed on the merozoite surface, as well as the surface of infected erythrocytes, may alter host cell tropism and contribute to the ability of malaria parasites to evade merozoite-specific, neutralizing antibodies.

Animals↗

PubMed1996

Influence of ORF2 on host cell tropism of feline immunodeficiency virus.

Feline immunodeficiency virus (FIV) is a lentivirus associated with an immunodeficiency syndrome of the domestic cat. A short open reading frame (ORF2), of unknown function, is present in all FIV isolates. We have investigated the role of ORF2 in determining the cell tropism of two infectious molecular clones of FIV. FIV-PPR is able to productively infect feline peripheral blood leukocytes (PBLs) and a T lymphocyte cell line (MCH5-4), but not a feline astrocyte cell line (G355-5) or Crandell feline kidney cells (CrFK). In contrast, FIV-34TF10 is able to productively infect G355-5 and CrFK cells, but not PBLs or MCH5-4 cells. The major difference in these FIV clones is that ORF2 in FIV-PPR is capable of encoding a 79-amino-acid peptide, whereas there is a stop codon in ORF2 after 43 amino acids in FIV-34TF10. We performed site-directed mutagenesis to change the stop codon (TGA) in FIV-34TF10 to a tryptophan (TGG), the amino acid present at this location in FIV-PPR. FIV-34TF10 with ORF2 repaired (FIV-ORF2rep) productively infected PBLs, MCH5-4 cells, and primary macrophages, as well as CrFK and G355-5 cells, indicating that a protein encoded by ORF2 plays a role in determining the host cell tropism of FIV. ORF2 contains hydrophobic, acidic, and leucine-rich domains similar to those shown to be important for transactivating proteins of other lentiviruses. Coexpression of a plasmid expressing the ORF2 gene product with another construct expressing the chloramphenicol acetyl transferase (CAT) gene driven by the FIV LTR, resulted in transactivation of CAT expression in both feline and human cells.

Amino Acid Sequence↗

PubMed1997

Abortive infection in HeLaCD4 cells by a primary HIV type 1 isolate: implications for differential host cell tropism.

The emergence of T cell-tropic, syncytium-inducing (T-tropic/SI) HIV-1 variants from the background of macrophage-tropic, non-syncytium-inducing (M-tropic/NSI) strains is associated with disease progression in infected individuals. HIV89.6 is a primary isolate with a transitional phenotype: like M-tropic strains it replicates in primary macrophages and lymphocytes but not in most transformed cells, yet it is also syncytium inducing. We have shown that HIV89.6 can utilize both the M-tropic and T-tropic cofactors CCR-5 and CXCR-4, respectively, in conjunction with CD4 for fusion and entry into otherwise nonpermissive nonhuman cells. To better understand the nature of restricted HIV89.6 infection of transformed cells, we analyzed its interaction with CD4-expressing transformed human HeLaCD4-LTR/beta-Gal cells, which contain the beta-galactosidase gene linked to the HIV-1 LTR. Here we show that HIV89.6 enters these cells and undergoes reverse transcription and integration. Furthermore, HIV89.6 induces LTR-driven beta-galactosidase expression, indicating Tat-dependent trans-activation, in a similar number of cells as the permissive T-tropic/SI isolate HIV(HXB). Acute infection with HIV89.6, however, produces markedly lower levels of p24 antigen and infectious virus per trans-activation-positive cell than HIV(HXB). In contrast, transfection results in high levels of expression for both viruses but HIV89.6 still fails to establish spreading infection. HIV89.6 is also blocked after entry in two other nonpermissive cell lines, SUP-T1 and U937. HIV89.6 arrest in HeLaCD4-LTR/beta-Gal cells at a stage subsequent to entry, reverse transcription, integration, and Tat expression is a novel level at which HIV-1 strain- and cell-specific restrictions define host cell tropism. These studies emphasize that complex patterns of tropism are determined by the interplay of permissive or restricted virus-cell interactions at multiple steps in the replication cycle.

Antibodies, Monoclonal↗

PubMed1992

Canine and feline host ranges of canine parvovirus and feline panleukopenia virus: distinct host cell tropisms of each virus in vitro and in vivo.

Canine parvovirus (CPV) emerged as an apparently new virus during the mid-1970s. The origin of CPV is unknown, but a variation from feline panleukopenia virus (FPV) or another closely related parvovirus is suspected. Here we examine the in vitro and in vivo canine and feline host ranges of CPV and FPV. Examination of three canine and six feline cell lines and mitogen-stimulated canine and feline peripheral blood lymphocytes revealed that CPV replicates in both canine and feline cells, whereas FPV replicates efficiently only in feline cells. The in vivo host ranges were unexpectedly complex and distinct from the in vitro host ranges. Inoculation of dogs with FPV revealed efficient replication in the thymus and, to some degree, in the bone marrow, as shown by virus isolation, viral DNA recovery, and Southern blotting and by strand-specific in situ hybridization. FPV replication could not be demonstrated in mesenteric lymph nodes or in the small intestine, which are important target tissues in CPV infection. Although CPV replicated well in all the feline cells tested in vitro, it did not replicate in any tissue of cats after intramuscular or intravenous inoculation. These results indicate that these viruses have complex and overlapping host ranges and that distinct tissue tropisms exist in the homologous and heterologous hosts.

Animals↗

PubMed1992

Risks connected with the use of conventional and genetically engineered vaccines.

A review is given of real and potential risks connected with the use of conventional and genetically engineered live and dead vaccines. Special attention is given to live carrier vaccines expressing one or more heterologous genes of other microorganisms. Because most carrier vaccines are still in an experimental phase, there is only limited experience with the risks of carrier vaccines. There are three potential risks of live carrier vaccines which will be discussed: 1. Changes in cell, tissue, of host tropism, and virulence of the carrier through the incorporation of foreign genes. 2. Exchange of genetic information with other vaccine or wild-type strains of the carrier organism. 3. Spread in the environment. Only limited experimental data are available on changes in biological behaviour of microorganisms through the incorporation of foreign genes. For example, there are indications that vaccinia virus carrying the attachment protein G of respiratory syncytial virus (RSV) replicates better in lungs of mice than vaccinia virus carrying other genes of RSV. Poxviruses carry genes that probably determine their replication in different hosts. Exchange of such host tropism genes might alter their host spectrum. Recombination between herpesvirus vaccine or wild-type strains may lead to the appearance of virulent strains with of without heterologous genes. Before carrier vaccines are applied, these risks must be thoroughly evaluated case-by-case. Potential methods for the design of safe carrier vaccines are discussed.

Animals↗