Structural Research of Retroviridae

The Retroviridae comprise two subfamilies and eleven genera that are widespread and infect a wide range of vertebrates. Retroviridae comprises a wide range of RNA viruses, including the human immunodeficiency virus (HIV) that causes acquired immunodeficiency syndrome (AIDS). Retroviruses are uniquely characterized by the potential to reverse transcribe their RNA genome into DNA, integrate into the host genome, and establish persistent infections. These viruses can have serious consequences for human and animal health, leading to immunodeficiency, cancer, and other debilitating diseases. In recent years, advances in structural and molecular techniques have made it possible to better understand retroviruses, including how they regulate and coordinate the different steps of the viral life cycle, with essential implications for the development of vaccines and antiviral drugs.

Figure 1. 3D structure of HIV.

Composition of Retroviruses Virus Particles

Retroviruses virus particles are enveloped spherical, 80-100 nm diameter with 8 nm glycoprotein spikes.

Virus particle composition:

• Envelope: composed of lipids (obtained from the host plasma membrane during germination) and glycoproteins encoded by the env gene.
• RNA: consists of dimeric RNA with a cap at the 5' end and a poly (A) tail at the 3' end. Genomic RNA (gRNA) is the result of host RNA polymerase II (Pol II) activity and is processed into host mRNA by the addition of a 5' methyl cap and a 3' poly A tail.
• Proteins: include gag proteins, proteases (PR), pol proteins, and env proteins. The group-specific antigen (gag) proteins are the main components of the viral capsid and specifically recognize, bind, and package retroviral genomic RNA into assembled virions. Pol proteins are responsible for synthesizing viral DNA and integrating it into host DNA after infection. Env proteins play a role in viral particle binding and entry into the host cell.

Advances in the Structural Research of Retroviruses

Electron microscopy plays an essential role in the morphological characterization of individual retroviruses, the results of which form the basis of the retrovirus. In recent years, researchers have used single-particle cryo-electron microscopy (cryo-EM) to capture information on the core structural protein (CA) details of HML2, a newly acquired human endogenous retrovirus, at 2.7 to 4.3 Å resolution. Most species contain 12 HML2 CA^rec pentamers showing T = 1 icosahedral symmetry. These icosahedral and podoplanar assemblies reveal at high resolution the molecular interactions that allow CA to form pentamers and hexamers.

Figure 2. Structure of HML2 CA^rec monomer and assembled particles. (Acton O, et al, 2019)

Viral structure elucidation helps to improve the understanding of the virus's molecular structure and its interactions with hosts. It plays a critical role in antiviral research, facilitating the development of innovative therapeutic strategies and the identification of potential drug targets. In addition, virus structural analysis helps enhance clients' understanding of viral evolution and drug resistance, which promotes vaccine design and development.

Creative Biostructure is at the forefront of viral structure elucidation and offers a wide range of high-purity virus-like particles (VLPs). Our products are morphologically identical or similar to real virus particles and can efficiently self-assemble, which facilitates basic research on viruses and the discovery of vaccines.

With a high-resolution electron microscopy (EM) platform, Creative Biostructure can provide structural analysis services for a wide range of viruses. Our scientists have the expertise and necessary skills to reveal the complex structures of viruses and help clients develop antiviral drugs and vaccines.

We are committed to providing a personalized service to satisfy the goals and research priorities of each client. If you are interested in our services or products, please contact us. We look forward to working with you.

References

1. Acton O, et al. Structural basis for Fullerene geometry in a human endogenous retrovirus capsid. Nat Commun. 2019. 10(1): 5822.
2. Coffin J, et al. ICTV Virus Taxonomy Profile: Retroviridae 2021. J Gen Virol. 2021. 102(12): 001712.
3. Krebs AS, et al. Structural Analysis of Retrovirus Assembly and Maturation. Viruses. 2021. 14(1): 54.