The key amino acid sites 199–205, 269, 319, 321 and 324 of ALV-K env contribute to the weaker replication capacity of ALV-K than ALV-A

Abstract

Background Avian leukosis virus (ALV) is an infectious retrovirus, that mainly causes various forms of tumours, immunosuppression, a decreased egg production rate and slow weight gain in poultry. ALV consists of 11 subgroups, A–K, among which ALV-K is an emerging subgroup that has become prevalent in the past 10 years. Most ALV-K isolates showed weak replication ability and pathogenicity. In this study, the weak replication ability of ALV-K was explored from the perspective of the interaction between ALV-K gp85 and the Tva receptor. Methods Fourteen soluble recombinant ALV-A/K gp85 chimeric proteins were constructed by substituting the sequence difference regions (hr1, hr2 and vr3) of the ALV-A gp85 protein with the skeleton ALV-K gp85 protein for co-IP and competitive blocking tests. Results The binding capacity of ALV-K gp85 to Tva was significantly weaker than that of ALV-A gp85 (P < 0.05) and the key amino acid sites 199–205, 269, 319, 321 and 324 of ALV-K env contributed to the weaker replication capacity of ALV-K than ALV-A. Conclusions This is the first study to reveal the molecular factors of the weak replication ability of ALV-K from the perspective of the interaction of ALV-K gp85 to Tva, providing a basis for further elucidation of the infection mechanism of ALV-K.

The phylogenetic analysis of the new emerging ALV-K revealing the co-prevailing of multiple clades in chickens and a proposal for the classification of ALV-K

“…In general, early isolates of ALV-K exhibited no or low pathogenicity. Chen et al (13) reported that key aa sites 199-205, 269, 319, 321, and 324 of ALV-K env contributed to the weaker replication capacity of ALV-K than that of ALV-A. This is the first time that molecular factors for the weak replicative ability of ALV-K have been revealed.…”

“…These newly discovered ALV-K strains could be adapting in the Chinese local chickens, increasing their prevalence and pathogenicity in flocks. In addition, for routine eradication and diagnostic assays, the presence of ALV-K is not easily detected due to its slow replication compared to other subgroups and the fact that it is only cultured on cells for one passage, thus making it easy to miss detection (12)(13)(14). This virus may have existed in Chinese local chickens for a long time and probably as a persistent infection without notice, due to its weak replication ability (12,14).…”

Avian Leukosis: Will We Be Able to Get Rid of It?

“…ALV-A and ALV-B are recognized ALV-K is the most recently characterized subgroup. It was first identified in South China in 2012 in yellow broilers and it was determined that it caused a milder disease than other subgroups [57], which may be due to decreased LTR promoter activity [58] or a weaker binding capacity of ALV-K gp85(SU) to its receptor, Tva [59]. Nucleotide sequence analysis of viruses in this subgroup shows that the gag and pol genes have high sequence similarity (>94%) to those of ALV-A through ALV-E and ALV-J (especially to those of ALV-E, 96%) [58], but may be as low as 44% for ALV-J gp37(TM), contrarily to gp85(SU), which shows low sequence similarity with that of other subgroups (<87% to ALV-A to E and <20% to ALV-J) [58,60].…”

“…ALV from the different subgroups tends not to cross-neutralize, except for partial cross-neutralization between subgroups B and D [94,95]. A variety of studies have identified hr1 (aa194-198 and aa206-216) and hr2 (aa251-256 and aa269-280) as the main binding domains between the viral gp85 (SU) and the host protein receptor [59,96], with vr3 contributing to the specificity of the receptor interaction for initiating efficient infection [97]. Thus, polymorphisms in hr1 and hr2 regions may determine susceptibility due to increased or decreased binding capability, with the possibility that different or new subgroups of the virus arise if the hr regions bind to a different chicken cell surface protein [21].…”

“…Subsequent epidemiological investigation revealed that ALV-K was widespread among Chinese native chickens [43]. Most ALV-K were isolated from apparently healthy individuals, but some variants are significantly pathogenic [55,59,60,123,124].…”