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HIV's secret weapon: Why are two RNAs more powerful than one?
Since the HIV virus was discovered in 1983, the genome and proteins of the human immunodeficiency virus have been the subject of extensive research. At one time, people mistakenly believed that the virus was a form of human T-cell leukemia virus (HTLV), which is known to affect the human immune system and cause certain leukemias. However, researchers from the Pasteur Institute in Paris isolated a previously unknown retrovirus with a different genetic structure from AIDS patients, which was later named HIV.
The HIV virus particle consists of a viral envelope and associated matrix surrounding an inner core, which itself encloses two copies of the single-stranded RNA genome and several enzymes.
These technological advances have enabled scientists to gain a deeper understanding of HIV's structure. The complete genome sequence of HIV-1 has been resolved to single nucleotide accuracy. The HIV genome encodes a small number of viral proteins that establish cooperative relationships among themselves and between HIV and host proteins in order to invade host cells and hijack their internal machinery. The structure of HIV is significantly different from other retroviruses.
Structure of HIV
HIV virus particles are approximately 100 nanometers in diameter, and their innermost part consists of a conical core containing two positive-sense single-stranded ssRNA genomes, the enzymes reverse transcriptase, integrase and protease, as well as other minor proteins and Major core protein. The HIV genome is 9749 nucleotides long and has a cap structure at the 5’ end and a poly(A) tail at the 3’ end.The viral core structure consists of two non-covalently linked unspliced positive-sense single-stranded RNAs that are usually identical.
One of the keys is why HIV packages two RNAs instead of just one, which has multiple advantages. First, these two RNAs facilitate the recombination of HIV-1 during reverse transcription, thereby increasing genetic diversity. Additionally, when the reverse transcriptase encounters a break in the viral RNA, the presence of the two RNAs allows it to switch between templates, thus completing reverse transcription without loss of genetic information.
However, this dimeric RNA genome may also play a structural role in viral replication. The RNA components encapsulated in the virus not only provide diversity, but also ensure the consistency and integrity of the virus's work.
Genome organization
HIV has several major genes that encode structural proteins common to all retroviruses and some non-structural ("accessory") genes that are unique to HIV. The HIV genome contains nine genes encoding fifteen viral proteins, which are synthesized as polyproteins.
The HIV genome produces nine different gene products from a genome of less than 10 kb through a differential RNA splicing system.
After synthesis, these proteins enter the interior of the virus particle. Among them, the gag gene is responsible for the basic physical basis, while the pol gene provides the basic mechanism of retroviral reproduction. The presence of these important genes enables HIV to effectively enter host cells and promote its own replication.
HIV regulatory elementsThe regulatory system of HIV-1 is highly complex and includes some important regulatory genes, such as Tat and Rev. Tat is highly interdependent with the reverse transcription process of HIV, and its main function is to ensure the efficient synthesis of viral mRNA. Rev ensures the synthesis of HIV's main proteins and is essential for viral replication.
These regulatory proteins significantly affect the HIV life cycle by influencing RNA structure and dramatically changing the process of reverse transcription.
Similarly, auxiliary regulatory proteins such as Vpr, Vif, and Nef also play a key role in the virus's ability to spread. The multifunctional nature of these accessory proteins enables HIV to adapt and survive in different environments and is part of its ability to continuously mutate.
Secondary structure of RNA
Several conserved secondary structural elements have been identified in the HIV RNA genome that play a key role in the reverse transcription process, including the 5' end and multiple secondary structures such as the TAR element and the HIV Rev response. Element (RRE). These structures have a profound impact on the life cycle of HIV.HIV's RNA secondary structure is thought to play an important role in regulating HIV replication, helping the virus to move through the various stages of its life cycle more efficiently.
With advances in structural biology, scientists are gaining a deeper understanding of HIV, and those advanced technologies have shown great potential in vaccine development and treatment methods.
The replication mechanism of HIV and how it adapts and mutates will undoubtedly remain a hot topic for future research. As research deepens, whether we can find a long-lasting and effective vaccine or treatment remains a thought-provoking question.
