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Two functionally distinct forms of a retroviral receptor explain the nonreciprocal receptor interference among subgroups B, D, and E avian leukosis viruses.

Subgroups B, D, and E avian leukosis viruses (ALV-B, -D, and -E) share the same chicken receptor, TVB(S1), a tumor necrosis factor receptor (TNFR)-related protein. These viruses, however, exhibit nonreciprocal receptor interference (NRI): cells preinfected with ALV-B or ALV-D are resistant to superinfection by viruses of all three subgroups, whereas those pre-infected by ALV-E are resistant only to superinfection by other subgroup E viruses. In this study, we investigated the basis of this phenomenon by characterizing the interaction of TVB(S1) with ALV-B Env or ALV-E Env. Sequential immunoprecipitation analysis using surface envelope immunoglobulin fusion proteins revealed the existence of two separate types of TVB(S1) that are encoded by the same cDNA clone. One form, designated the type 1 receptor, is specific for ALV-B and ALV-E. The other form, the type 2 receptor, is specific for ALV-B. We show that a protein consisting of only the first and second extracellular cysteine-rich domains of TVB(S1) is capable of forming both receptor types. However, the third extracellular cysteine-rich domain is required for efficient formation of the type 1 receptor. We also demonstrate that heterogeneous N-linked glycosylation cannot explain the difference in activities of the two receptor types. The existence of two types of TVB(S1) explains the NRI pattern between ALV-B and -E: subgroup B viruses establish receptor interference with both receptor types, whereas subgroup E viruses interfere only with the type 1 receptor, leaving the type 2 receptor available to mediate subsequent rounds of ALV-B entry. The formation of a TVB receptor type that is specific for cytopathic ALV may also have important implications for understanding how some subgroups of ALV cause cell death.

Amino Acid Sequence↗

Genetic variability and molecular evolution of the human respiratory syncytial virus subgroup B attachment G protein.

Human respiratory syncytial virus (HRSV) is the most important cause of acute respiratory disease in infants. Two major subgroups (A and B) have been identified based on antigenic differences in the attachment G protein. Antigenic variation between and within the subgroups may contribute to reinfections with these viruses by evading the host immune responses. To investigate the circulation patterns and mechanisms by which HRSV-B viruses evolve, we analyzed the G protein genetic variability of subgroup B sequences isolated over a 45-year period, including 196 Belgian strains obtained over 22 epidemic seasons (1982 to 2004). Our study revealed that the HRSV-B evolutionary rate (1.95 x 10(-3) nucleotide substitutions/site/year) is similar to that previously estimated for HRSV-A (1.83 x 10(-3) nucleotide substitutions/site/year). However, natural HRSV-B isolates appear to accommodate more drastic changes in their attachment G proteins. The most recent common ancestor of the currently circulating subgroup B strains was estimated to date back to around the year 1949. The divergence between the two major subgroups was calculated to have occurred approximately 350 years ago. Furthermore, we have identified 12 positively selected sites in the G protein ectodomain, suggesting that immune-driven selective pressure operates in certain codon positions. HRSV-A and -B strains have similar phylodynamic patterns: both subgroups are characterized by global spatiotemporal strain dynamics, where the high infectiousness of HRSV permits the rapid geographic spread of novel strain variants.

Amino Acid Sequence↗

The receptor for the subgroup C avian sarcoma and leukosis viruses, Tvc, is related to mammalian butyrophilins, members of the immunoglobulin superfamily.

The five highly related envelope subgroups of the avian sarcoma and leukosis viruses (ASLVs), subgroup A [ASLV(A)] to ASLV(E), are thought to have evolved from an ancestral envelope glycoprotein yet utilize different cellular proteins as receptors. Alleles encoding the subgroup A ASLV receptors (Tva), members of the low-density lipoprotein receptor family, and the subgroup B, D, and E ASLV receptors (Tvb), members of the tumor necrosis factor receptor family, have been identified and cloned. However, alleles encoding the subgroup C ASLV receptors (Tvc) have not been cloned. Previously, we established a genetic linkage between tvc and several other nearby genetic markers on chicken chromosome 28, including tva. In this study, we used this information to clone the tvc gene and identify the Tvc receptor. A bacterial artificial chromosome containing a portion of chicken chromosome 28 that conferred susceptibility to ASLV(C) infection was identified. The tvc gene was identified on this genomic DNA fragment and encodes a 488-amino-acid protein most closely related to mammalian butyrophilins, members of the immunoglobulin protein family. We subsequently cloned cDNAs encoding Tvc that confer susceptibility to infection by subgroup C viruses in chicken cells resistant to ASLV(C) infection and in mammalian cells that do not normally express functional ASLV receptors. In addition, normally susceptible chicken DT40 cells were resistant to ASLV(C) infection after both tvc alleles were disrupted by homologous recombination. Tvc binds the ASLV(C) envelope glycoproteins with low-nanomolar affinity, an affinity similar to that of binding of Tva and Tvb with their respective envelope glycoproteins. We have also identified a mutation in the tvc gene in line L15 chickens that explains why this line is resistant to ASLV(C) infection.

Amino Acid Sequence↗

Bence Jones proteins and light chains of immunoglobulins. Preferential association of the V lambda VI subgroup of human light chains with amyloidosis AL (lambda).

An antiserum prepared against a lambda-Bence Jones protein from a patient (SUT) who had multiple myeloma and amyloidosis had specificity for lambda-light chains of the chemically defined variable (V) region lambda-chain subgroup lambda VI. Sequence analyses of protein SUT and of five other lambda-light chains recognized immunologically as of the V lambda VI subgroup revealed that all six proteins had the N-terminal sequence characteristic for prototype lambda VI proteins. The isotypic nature of the V lambda VI subgroup was demonstrated immunochemically: lambda VI molecules were detected among light chains isolated from the IgG proteins of each of 12 normal individuals and lambda VI antigenic determinants were also detectable on the intact IgG proteins. The frequency of lambda VI molecules among lambda-type light chains is estimated to be approximately 5% based on the finding that 5 of 91 lambda Bence Jones proteins were of the V lambda VI subgroup. Proteins of the V lambda VI subgroup, in contrast to those of the other five chemically-classified lambda chain subgroup, appear to be preferentially associated with the amyloid process as evidenced by the fact that all six lambda VI proteins were obtained from patients with amyloidosis AL and, in addition, 5 of 42 lambda-type monoclonal immunoglobulins from patients with primary or myeloma-associated amyloidosis were classified by immunodiffusion analyses as having lambda VI-type light chains.

Amino Acid Sequence↗

Defining subgroups of dual diagnosis patients for service planning.

OBJECTIVE: The high proportion of persons presenting for treatment of psychiatric disorders who also have comorbid substance use problems severely challenges the capacity of mental health care programs to plan for patients' needs. One of the problems encountered in anticipating the treatment needs of these patients is the wide heterogeneity of their comorbidity, that is, the broadly varying types, severity, and time courses of psychiatric and substance disorders. This paper describes and evaluates a relatively simple conceptual framework for delineating the heterogeneity of patients who are dually diagnosed. METHODS: A typology of subgroups of patients was defined a priori based on whether patients are singly or dually diagnosed and whether their disorders are current or past. Patients admitted to three treatment facilities in an inner-city catchment area were assigned to one of the subgroups based on administration of the Structured Clinical Interview for DSM-III-R-Patient Version (SCID-P). The subgroups were compared on clinical diagnoses and service needs as measured by the SCID-P and the Addiction Severity Index. RESULTS: A total of 461 patients were assigned to four mutually exclusive dual diagnosis subgroups--patients with current definite dual diagnoses, current possible dual diagnoses, current substance-induced organic mental disorder, and past definite dual diagnoses--and the two comparison groups. The subgroups differed significantly from each other and from two single-diagnosis comparison groups on axis I diagnoses, types of substance use disorders, and current problem areas. CONCLUSIONS: The framework developed has potential utility for distinguishing subgroups of dually diagnosed patients relevant for service planning.

Adult↗

Use of tree-based models to identify subgroups and increase power to detect linkage to cardiovascular disease traits.

BACKGROUND: Our goal was to identify subgroups of sib pairs from the Framingham Heart Study data set that provided higher evidence of linkage to particular candidate regions for cardiovascular disease traits. The focus of this method is not to claim identification of significant linkage to a particular locus but to show that tree models can be used to identify subgroups for use in selected sib-pair sampling schemes. RESULTS: We report results using a novel recursive partitioning procedure to identify subgroups of sib pairs with increased evidence of linkage to systolic blood pressure and other cardiovascular disease-related quantitative traits, using the Framingham Heart Study data set provided by the Genetic Analysis Workshop 13. This procedure uses a splitting rule based on Haseman-Elston regression that recursively partitions sib-pair data into homogeneous subgroups. CONCLUSIONS: Using this procedure, we identified a subgroup definition for use as a selected sib-pair sampling scheme. Using the characteristics that define the subgroup with higher evidence for linkage, we have identified an area of focus for further study.

Adolescent↗

Assessing subgroup effects with binary data: can the use of different effect measures lead to different conclusions?

BACKGROUND: In order to use the results of a randomised trial, it is necessary to understand whether the overall observed benefit or harm applies to all individuals, or whether some subgroups receive more benefit or harm than others. This decision is commonly guided by a statistical test for interaction. However, with binary outcomes, different effect measures yield different interaction tests. For example, the UK Hip trial explored the impact of ultrasound of infants with suspected hip dysplasia on the occurrence of subsequent hip treatment. Risk ratios were similar between subgroups defined by level of clinical suspicion (P = 0.14), but odds ratios and risk differences differed strongly between subgroups (P < 0.001). DISCUSSION: Interaction tests on different effect measures differ because they test different null hypotheses. A graphical technique demonstrates that the difference arises when the subgroup risks differ markedly. We consider that the test of interaction acts as a check on the applicability of the trial results to all included subgroups. The test of interaction should therefore be applied to the effect measure which is least likely a priori to exhibit an interaction. We give examples of how this might be done. SUMMARY: The choice of interaction test is especially important when the risk of a binary outcome varies widely between subgroups. The interaction test should be pre-specified and should be guided by clinical knowledge.

Data Interpretation, Statistical↗

Differences in treatment outcome between subgroups of patients with chronic low back pain using lumbar dynamometry and psychological aspects.

OBJECTIVE: To investigate whether subgroups of patients with chronic low back pain show differences in treatment outcome, measured with the Roland Disability Questionnaire. (RDQ). SETTING: The study was carried out in a rehabilitation centre. SUBJECTS: Eighty-four patients with chronic low back pain participated in this study. INTERVENTION: Patients followed a multidisciplinary treatment programme that primarily targets physical aspects. DESIGN AND MAIN OUTCOME MEASURE: Based on pretreatment lumbar dynamometry results and Symptom Checklist (SCL-90) scores, patients were divided into subgroups. The dynamometry subgroups were: performances lower than healthy subjects (expected performance), performances comparable with those of healthy subjects (normal performance) and inconsistent performances (submaximal performance). The SCL-90 subgroups were: a total score of 'average' or lower compared with a population of chronic pain patients (low psychological score) and a total score of 'above average' or higher compared with this population (high psychological score). Patients answered the RDQ in the week before (RDQ1; n = 84) and after treatment (RDQ2; n = 78) to investigate whether the subgroups show differences in outcome expressed as the percentage change between RDQ2 and RDQ1, (%RDQ2-1). A %RDQ2-1 > or = 20% was classified as an improvement. RESULTS: Improvement on disability level > or = 20% is shown in 64% and 55% of the patients with 'normal' and 'expected' lumbar dynamometry performances and low psychological scores compared with only 33% and 25% of those with high psychological scores. Patients with submaximal performances show hardly any changes in disability level and there are no differences betweenthose with low psychological scores (14%) and those reporting high scores (0%). CONCLUSION: The fact that patient subgroups with differences in treatment outcome can be defined using lumbar dynamometry and psychological questionnaires suggests that these instruments might facilitate treatment indication in clinical practice.

Adult↗

Methodologic issues in terminating enrollment of a subgroup of patients in a multicenter randomized trial.

The National Emphysema Treatment Trial (NETT) was a multicenter randomized controlled trial comparing medical treatment plus lung-volume-reduction surgery (LVRS) to medical treatment alone for the treatment of severe emphysema. The primary outcomes specified for the trial were mortality from all causes and change in functional status as indicated by the change in maximum exercise capacity measured two years after randomization. A secondary objective of the trial was to define criteria to identify subgroups of patients at risk of harm or benefit from LVRS. Stopping guidelines for safety and efficacy based on 30-day mortality and a combination of overall mortality and functional status at two years were specified at the inception of the trial. Although specific subgroups of patients likely to benefit were not identified in advance, several clinical factors were specified as likely to be important in defining subgroups with differential outcome. In May 2001, with 40% of expected deaths accrued, the Data and Safety Monitoring Board determined that a subgroup of patients was at significantly higher risk of 30-day mortality from LVRS without counterbalancing evidence of functional benefit, and recommended that the protocol be modified to exclude further randomization of such patients. The trial's sponsor, the National Heart, Lung and Blood Institute, accepted the recommendation, which was rapidly communicated to participating clinics. This paper describes the operational aspects of identification of the subgroup and implementation of the recommendation to continue the trial, but to terminate enrollment of new patients in the subgroup. These aspects include notification of the investigators, the institutional review boards, the Research Group, the patients and the medical community. We also describe the repercussions of the publication and the misinterpretations of the results based on media coverage.

Clinical Protocols↗

High virus titer in feather pulp of chickens infected with subgroup J avian leukosis virus.

Subgroup J avian leukosis viruses (ALVs), which are a recombinant virus between exogenous and endogenous ALVs, can spread by either vertical or horizontal transmission. Exogenous and endogenous ALVs can be detected in feather pulp. In this study, virus titers in feather pulp of chickens infected with subgroup J ALV were compared with those of plasma and cloacal swab. All of the broiler chickens inoculated with subgroup J ALV at 1 day old were positive for virus from feather pulp during the experimental period of between 2 wk and 8 wk of age. Virus titers in feather pulp of some broiler chickens infected with subgroup J ALV were very high, ranging from 10(7) to 10(8) infective units per 0.2 ml. Virus titers in feather pulp were usually the highest among the samples of plasma, cloacal swab, and feather pulp tested. In another experiment in which layer chickens were inoculated with subgroup J ALV at 1 day old, virus was detected in feather pulp from 2 wk until 18 wk of age, and virus persisted longer in feather pulp than in plasma. Almost all of the layer chickens tested were positive for virus by polymerase chain reaction (PCR) with DNA extracted from feather pulp samples at 2, 4, and 10 wk of age, and the PCR from feather pulp was more sensitive than virus isolation from plasma, cloacal swab, and feather pulp. All above results indicate that samples of feather pulp can be useful for virus isolation and PCR to confirm subgroup J ALV infection.

Animals↗

Antigenic cross-reactivity among avian pneumoviruses of subgroups A, B, and C at the matrix but not nucleocapsid proteins.

Earlier findings from our laboratory based on analysis of nucleotide and predicted amino acid sequence identities of 15 avian pneumoviruses (APVs) isolated from the United States (subgroup C) demonstrated that the viruses were phylogenetically separated from the European subgroup A and subgroup B viruses. Here, we investigated whether viruses from the three subgroups were cross-reactive by testing field sera positive for each of the APV subgroups in an enzyme-linked immunosorbent assay (ELISA) test with recombinant matrix (M) and nucleoprotein (N) proteins generated from a Minnesota APV isolate (APV/MN2A). Sera from turkeys infected with APV subgroup A, B, or C reacted with recombinant M protein derived from APV/MN2A. In contrast, recombinant N protein from APV/MN2A virus was reactive with sera from subtypes A and C viruses but not from subtype B virus. The results illustrate that viruses from the three APV subtypes share antigenic homology, and the M protein-based ELISA is adequate for monitoring APV outbreaks but not for distinguishing between different subtypes.

Animals↗

Patterns of integration and expression of retroviral, non-replicative vectors in avian embryos: embryo developmental stage and virus subgroup envelope modulate tissue-tropism.

We previously demonstrated that Avian Leukemia Viruses (ALV) carrying the v-myc gene specifically induce two types of tumors, cardiomyocytic tumors when the virus is injected before embryonic day 3 (E3), skin tumors when the virus is injected at E3 or E5. Aiming to elucidate the mechanisms which determine this time-dependent change in target, we infected chick and quail embryos at E3 and E5 with replication-deficient, lacZ gene-carrying, ALV-based viruses produced by a packaging cell line. Three constructs driven by 3 different Long Terminal Repeats (LTRs) were tested and yielded similar results. When the constructs were inoculated at E3 and the lacZ gene product revealed 5 days later, around 70% of the embryos carried lacZ+ clones in the heart, around 50% had positive clones in the skin anywhere on the body, while a few embryos displayed clones in internal organs (liver, stomach, lungs). Immunocytological identification of the heart cell type(s) expressing the virus revealed that the only cells infected were cardiomyocytes. When the constructs were inoculated at E5, no lacZ+ clones appeared in the heart but all were located in the cephalic skin. In order to examine the relationship between viral integration and expression, DNA of different organs or tissues from lacZ stained embryos was analyzed by PCR. A tight correlation between integration and expression in the heart and in the skin was revealed in most cases. In contrast, a significant PCR signal was often detected in the liver or the stomach despite weak or absent expression as revealed by lacZ+ clones. We then investigated the influence of envelope glycoprotein subgroups on the tropism of these constructs. The lacZ vector driven by RAV-2 LTRs was packaged as subgroups A, B or E viral particles. The A subgroup, used in the part of the study described above, infects both chick and quail while the B and E subgroups are specific for chick or quail respectively. These B and E subgroups induced lacZ+ clones in the heart (after E3 injection) while no clones or only a few were detected in the skin either after E3 or E5 injection. The following conclusions can be drawn: 1) cardiomyocytes are at E3 the major target for integration and expression of ALV-derived viruses in vivo; 2) targets change rapidly with embryonic age; and 3) tissue-specific infections depend on the envelope subgroup, thus presumably on the presence of the cognate receptor.(ABSTRACT TRUNCATED AT 400 WORDS)

Alpharetrovirus↗

Detection of group- and subgroup-specific antigens of bovine rotaviruses in Bangladesh.

The study was carried out to detect group- and subgroup-specific antigens of bovine rotaviruses. Stool specimens, collected from diarrhoeic calves of the Savar Dairy Farm, Bangladesh, were examined by an enzyme-linked immunosorbent assay, using group- and subgroup-specific monoclonal antibodies. Thirty-three specimens showed specificity for group A rotavirus. While subgrouping, 21 group A-positive specimens showed subgroup I specificity. Twelve specimens did not react with either of the subgroup I- and subgroup II-specific monoclonal antibodies.

Animals↗

Impact of subgroup prevalences on partitioning of Gaussian-distributed reference values.

BACKGROUND: The aims of this report were to examine how unequal subgroup prevalences in the source population may affect reference interval partitioning decisions and to develop generally applicable guidelines for partitioning gaussian-distributed data. METHODS: We recently proposed a new model for partitioning reference intervals when the underlying data distribution is gaussian. This model is based on controlling the proportions of the subgroup distributions that fall outside each of the common reference limits, using the distances between the reference limits of the subgroup distributions as functions to these proportions. We examine the significance of the unequal prevalence effect for the partitioning problem and quantify it for distance partitioning criteria by deriving analytical expressions to express these criteria as a function of the ratio of prevalences. An application example, illustrating various aspects of the importance of the prevalence effect, is also presented. RESULTS: Dramatic shrinkage of the critical distances between reference limits of the subgroups needed for partitioning was observed as the ratio of prevalences, the larger one divided by the smaller one, was increased from unity. Because of this shrinkage, the same critical distances are not valid for all ratios of prevalences, but specific critical distances should be used for each particular value of this ratio. Although proportion criteria used in determining the need for reference interval partitioning are not dependent on the prevalence effect, this effect should be accounted for when these criteria are being applied by adjusting the sample sizes of the subgroups to make them correspond to the ratio of prevalences. CONCLUSIONS: The prevalences of subgroups in the reference population should be known and observed in the calculations for every reference interval study, irrespective of whether distance or proportion criteria are being used to determine the need for reference interval partitioning. We present detailed methods to account for the prevalences when applying each of these types of criteria. Analytical expressions for the distance criteria, to be used when high precision is needed, and approximate distances, to be used in practical work, are derived. General guidelines for partitioning gaussian distributed data are presented. Following these guidelines and using the new model, we suggest that partitioning can be performed more reliably than with any of the earlier models because the new model not only offers an improved correspondence between the critical distances and the critical proportions, but also accounts for the prevalence effect.

Biometry↗

Isolation of subgroup J avian leukosis virus in Korea.

Two subgroup J avian leukosis viruses (ALVs) were isolated from broiler breeder flocks, in which myeloid leukosis had occurred. The isolates could be classified as subgroup J ALV by the positive reaction in polymerase chain reaction (PCR) with primers specific for subgroup J ALV. Two isolates replicated in chicken embryo fibroblast (CEF) cells from the alv6 chicken line in which cells are resistant to subgroup A and E ALVs. In in vitro serum neutralization tests with other subgroup ALVs including ADOL-Hc1, the prototype of subgroup J ALVs isolated in the United States of America, two isolates were partially neutralized by antibody to ADOL-Hc1, indicating that Korean isolates and ADOL-Hc1 may be antigenically related, but not identical. When the PCR was done with a primer pair designed to amplify genes of E element and long terminal repeat of proviral DNA, the PCR product size of one isolate (KOAL-PET) was smaller than that of ADOL-Hc1, suggesting that some sequences in these regions are deleted.

Animals↗

[Identification of a novel B variant allele in a Chinese Han individual with B subgroup].

OBJECTIVE: To study the molecular genetic background of B subtype in Chinese Han population and identify novel allele at the ABO locus. METHODS: Ten samples from randomly selected blood donors of normal B phenotype used as control, and six samples from individuals diagnosed as B subgroup by serological tests were genotyped by sequence specific primer polymerase chain reaction and direct DNA sequencing at the exons 6 and 7 of ABO gene. The exons 6 and 7 and the intervening intron 6 of the B allele from each B subgroup sample were analyzed by cloning and haplotype sequencing. RESULTS: A novel B variant allele was identified in two individuals whose blood samples were diagnosed as belonging to Bx subgroup and Bw subgroup respectively, the novel B allele being different from the allele B101 by single 695T>C missense mutation in exon 7. A family with the individual possessed Bx subgroup was studied. Among 22 family members tested, seven family members were found to carry the novel B variant allele. No novel point mutation at the exons 6 and 7 of ABO gene were detected in the ten control samples and the other four samples with B subgroup. CONCLUSION: The present authors define this allele as a novel B variant allele. The mutation of this novel allele, in which the nucleotide alters from T to C at position of 695 in exon 7 and hence results in an amino acid change from Leu to Pro, is expected to diminish the enzyme's activity. It indicates that the alteration of amino acid at the position of 232 is critical to the activity of glycosyltransferases.

ABO Blood-Group System↗

Identification of a novel B variant allele at the ABO locus in Chinese Han individuals with B subgroup.

We studied the molecular genetic background of the B subgroup in the Chinese Han population and identified a novel allele at the ABO locus. Ten control samples from randomly selected blood donors of normal B phenotype and 6 samples from individuals diagnosed as B subgroup by serological tests were genotyped by PCR-SSP and direct DNA sequencing at exons 6 and 7 of the ABO gene. Exons 6 and 7 and the intervening intron 6 of B alleles from the 6 B subgroup samples were analyzed by cloning and haplotype-sequencing. A novel B variant allele was identified in 2 individuals who were serologically-determined as members of the B(x) and B(w) subgroups, respectively. The novel B allele differs from allele B101 by a single 695T>C missense mutation in exon 7. The family of the individual with B(x) subgroup was studied; among 8 family members tested, 4 had the novel B variant allele. No mutation at exon 6 or 7 of the ABO gene was detected in the 10 control samples or in the other 4 B subgroup samples. Mutation at position 695 where T is replaced by C results in an amino acid change from Leu to Pro, which is predicted to diminish B transferase activity. This indicates that alteration of the amino acid at position 232 is critical to the activity of glycosyltransferases.

ABO Blood-Group System↗

Relationship of E1 and E3 regions of human adenovirus 35 to those of human adenovirus subgroups A, C and D.

Cloned PstI fragments of human adenovirus 35 (AV35) genome were compared with the DNA of representatives of human adenovirus subgroups A (type 12), B (type 7), C (types 1, and 5), D (type 8), and E (type 4), using blot hybridization techniques. The E1b region of AV35 was found to be more distantly related to those of other subgroups than E1a regions sequences and examined by others. DNA hybridization was observed only between E1b of AV35 and the DNA of AV4, thus the recombinant constructed might be applied as B-subgroup-specific diagnostic probe. Common nucleotide sequences were detected within the E3 regions of serotypes 1, 4, 5, 7, 8, and 35. On the basis of inter-subgroup homology, and PstI-fragments it may be concluded, that the structure of E3 sequences of AV7 and AV35 DNA are closely related to those of AV3 DNA sequenced by Signäs et al. [18]. E4 regions were compared only of serotypes representing subgroups B, C, and D. These sequences were subgroup specific, similarly to E1b regions.

Adenovirus Early Proteins↗