Evolution of primate T-cell leukemia virus type 1 accessory genes and functional divergence of its antisense proteins

What is it about?

Primate T-cell leukemia virus type 1 (PTLV-1) is a category of viruses that includes human T-cell leukemia virus type 1 (HTLV-1) and simian T-cell leukemia virus type 1 (STLV-1). Originating in monkeys, this virus has crossed species barriers and transmitted to humans on multiple occasions in Asia and Africa over thousands of years. This study characterizes the genetic diversity of different PTLV-1 subtypes and examines their association with geographical locations and host species. It was found that while certain proteins (the so-called accessory proteins) are conserved in the most common human subtype (HTLV-1a subtype), some African and Asian subtypes have lost them. Interestingly, only STLV-1 strains found in chimpanzees and gorillas retain them all. Additionally, although the antisense proteins, HTLV-1 and STLV-1 bZIP factor (HBZ/SBZ) are conserved, they function differently across subtypes. These findings suggest that the acquisition of the accessory proteins through evolution may have enhanced viral adaptability to the host, while differences in HBZ/SBZ functionality across species could influence the pathogenicity of the virus in different hosts. These findings advance our understanding of PTLV-1’s pathogenic mechanisms and underscore the need for more complete STLV-1 sequences from diverse host species and comparative infectivity studies to clarify the evolution of PTLV-1.

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Photo by Jamie Haughton on Unsplash

Photo by Jamie Haughton on Unsplash

Why is it important?

HTLV-1 infects millions of people and can cause cancer and neurological disease, yet how it evolved to infect humans has remained unclear. This study reveals for the first time that, among all primate PTLV-1 strains, only the major human strain (HTLV-1a) and those from chimpanzees and gorillas retain all accessory and regulatory genes. This suggests that critical viral features were preserved in apes, including humans, potentially supporting the virus’s transmission, adaptation, and persistence. The study also finds that, although the HBZ/SBZ protein is conserved across strains, its function varies. Notably, HBZ/SBZ from cosmopolitan HTLV-1a and African PTLV-1 strains strongly activate the TGF-β/Smad signaling pathway, which drives the proliferation of infected cells. Importantly, HBZ/SBZ from certain strains can also synergize with the host’s APOBEC3G protein to further enhance this pathway. These findings offer important insight into how HTLV-1/STLV-1 evolved to become more infectious and pathogenic in certain hosts.