The complete DNA sequence and genomic organization of the avian adenovirus CELO

Abstract

The complete DNA sequence of the avian adenovirus chicken embryo lethal orphan (CELO) virus (FAV-1) is reported here. The genome was found to be 43,804 bp in length, approximately 8 kb longer than those of the human subgenus C adenoviruses (Ad2 and Ad5). This length is supported by pulsed-field gel electrophoresis analysis of genomes isolated from several related FAV-1 isolates (Indiana C and OTE). The genes for major viral structural proteins (IIIa, penton base, hexon, pVI, and pVIII), as well as the 52,000-molecular-weight (52K) and 100K proteins and the early-region 2 genes and IVa2, are present in the expected locations in the genome. CELO virus encodes two fiber proteins and a different set of the DNA-packaging core proteins, which may be important in condensing the longer CELO virus genome. No pV or pIX genes are present. Most surprisingly, CELO virus possesses no identifiable E1, E3, and E4 regions. There is 5 kb at the left end of the CELO virus genome and 15 kb at the right end with no homology to Ad2. The sequences are rich in open reading frames, and it is likely that these encode functions that replace the missing E1, E3, and E4 functions.

Xenogenic Adenoviral Vectors

“…The packaging signal for atadenoviruses has not been defined but it may incorporate the ~160-bp region between the C-terminus of p32 K and the ITR. For the aviadenoviruses, ORFs with homologies to dUTPase and the REP protein of adeno-associated virus have been found [23] but there are distinct differences between FAdVl and FAdV8 with three of eight ORFs in the left end being unique to FAdVS [74]. It was also reported recently [83] that the cysteines and several other residues in the conserved sequence motif of E4 ORF6 are conserved in FAdVl ORF14, which lies near the left end of the genome [23].…”

“…For most other xenogenic AdVs no primary receptor has been characterized, nor is it clear whether secondary receptors such as integrins [21] are involved in virus uptake. Indeed, xenogenic AdVs lack identifiable or functionally confirmed integrin-binding sequences in their penton proteins [22][23][24][25][26][27]. For fiber, the coiled coil, trimeric structure of the stalk [28] is conserved, but the distinct sequences of the cell binding domains for the avi and atadenoviruses suggest that they utilize primary receptors that are distinct from CAR.…”

“…Of the xenogenic mastadenoviruses, complete nucleotide sequences have been determined for bovine (BAdV2 and 3) [24], porcine (PAdV3) [46], murine (MAdVl) [27], canine viruses (CAdVl and 2) [26], and simian viruses [20] ( Table I). For the aviadenoviruses, FAdVl [23] was the first genome sequenced but FAdV8 [47] is now also completed. Among the atadenoviruses, ovine (OAdV7) [22], bovine (BAdV4) (B. Harrach, pers.…”

“…Except for PAdV3 [46] and SAdVs [53], these are not present in xenogenic mastadenoviruses or OAdV7 [54], but a single copy is present near the right-hand end of FAdVl [55] and DAdVl ( Fig. 1) [23,48].…”

“…The extreme right ends of the avi-and atadenovirus genomes carry genes that are species specific. For example, DAdVl has numerous ORFs of unknov^n function that have no counterpart in OAdV7 [22,23,48,75]. Within the right-hand-end region of OAdV7 lies a series of six short reading frames (RHl to RH6) ( Fig.…”