Diversity of endogenous avian leukosis virus subgroup E (ALVE) insertions in indigenous chickens

Abstract

Background: Avian leukosis virus subgroup E (ALVE) insertions are endogenous retroviruses (ERV) that are restricted to the domestic chicken and its wild progenitor. In commercial chickens, ALVE are known to have a detrimental effect on productivity and provide a source for recombination with exogenous retroviruses. The wider diversity of ALVE in non-commercial chickens and the role of these elements in ERV-derived immunity (EDI) are yet to be investigated.

Results: In total, 974 different ALVE were identified from 407 chickens sampled from village populations in Ethiopia, Iraq, and Nigeria, using the recently developed obsERVer bioinformatics identification pipeline. Eighty-eight percent of all identified ALVE were novel, bringing the known number of ALVE integrations to more than 1300 across all analysed chickens. ALVE content was highly lineage-specific and populations generally exhibited a large diversity of ALVE at low frequencies, which is typical for ERV involved in EDI. A significantly larger number of ALVE was found within or near coding regions than expected by chance, although a relative depletion of ALVE was observed within coding regions, which likely reflects selection against deleterious integrations. These effects were less pronounced than in previous analyses of chickens from commercial lines.

Conclusions: Identification of more than 850 novel ALVE has trebled the known diversity of these retroviral elements. This work provides the basis for future studies to fully quantify the role of ALVE in immunity against exogenous ALV, and development of programmes to improve the productivity and welfare of chickens in developing economies.

Fig. 1

The diverse impacts of endogenous retroviruses. Intact endogenous retroviruses (ERV) share a conserved archetypal structure of retroviral proteins (gag, pol and env) enclosed by two long terminal repeats (LTR) which are identical at the point of integration in the host genome. ERV integration site largely determines its immediate impact on the host, as integration within or near genes may modulate host gene expression and facilitate continued ERV expression of retroviral gene products or intact virions, which can elicit persistent physiological stress on the host. As ERV copy number increases in the genome, ERV recombination facilitates intra- and interchromosomal rearrangements and acts as recipient sequence for recombination with related exogenous retroviruses (XRV)

Fig. 2

t-SNE visualisation of the ALVE-resolved population structure of the sampled chicken populations. Dimension reduction was performed on a binary matrix of ALVE shared between at least two individuals (n = 581). Samples from each country are coloured black for Ethiopia, red for Iraq and blue for Nigeria. t-SNE was derived using sci-kit learn with Python 3.7 with a learning rate of 15, perplexity of 65, and a maximum of 10,000 iterations to ensure stability

Fig. 3

ALVE distribution relative to coding features and randomly simulated integrations. Observed values represent all ALVE identified in this study (n = 974). Simulated values show the mean and standard deviation of one million randomly simulated redistributions of 974 integrations across the Galgal5 assembly. There was a significant depletion (P = 1.74 × 10⁻¹⁴) of integrations within coding regions (CR) and significant enrichment (P = 7.16 × 10⁻¹⁹) of integrations within 10 kb of CR. All other distance bins had non-significant differences. Specific values are reported in Additional file 2: Table S4