Science: For the first time, scientists are reconstructing HIV replication and integration in-body, with virus "protective shells" or therapeutic breakthroughs.

The human immunodeficiency virus (HIV), or AIDS virus, is a virus that causes defects in the human immune system.
, antiretroviral therapy (ART) has been used to inhibit viral replication by blocking the action of viral enzymes, winning a 3-line life for people living with HIV.
, of course, drug resistance problems follow.
While the proposed "cocktail therapy" (highly effective antiretroviral therapy, HAART) offers a new way out of the single ART drug resistance problem, scientists are also exploring whether there are other therapies that can bring AIDS patients to life. On October 9th researchers at the University of Virginia and the University of Utah published an article in Science entitled "Reconstitution and visualization of HIV-1 capsid-dependent complex and integration in vitro", which for the first time revealed the first step in HIV-infected host cells in vitro by building a cellless system - how the virus reverses and integrates in turn, and provides direct evidence that the viral shell is an important component of HIV infection.
Wesley I. Sundquist, a professor in the Department of Biochemistry at the University of Utah School of Medicine, said, "We're learning new knowledge about one of the most important pathogens that humans encounter, and it's important to help us understand how HIV infects host cells."
" HIV is a single-stranded RNA virus that, in order to infect host cells, the single-stranded RNA genome must be reversed by reverse transcriptase as a copy of double-stranded DNA and integrated into the host chromosome.
Although scientists have represented these two processes through a series of structural, bio-chemical, and molecular virological analyses, it is difficult to study the mechanisms of viral particles outside the cell because they are deep in the cytonite and nucleus.
in-body reconstruction and visualization of HIV-1 shell-dependent replication and integration to overcome this difficulty, researchers reconstructed these processes in cellless systems using purified HIV-1 virus particles as a source of virus genomes and enzymes.
First, by using a perforated peptide that allows HIV-1 to penetrate the viral envelope slightly, then adding deoxynucleotide triphosphate (dNTPs) initiates the endo-reverse transcription (ERT) process, and then adding cell extracts to simulate the process by which viral DNA is integrated into the external DNA.
depth sequencing and cloning analysis showed that the accumulation of double-stranded DNA occurred in this cellless system, and that viral DNA was integrated in the same way as HIV-infected cells.
, the HIV virus looks like a round egg roll ice cream, with hexagonal lattic coats wrapping the virus's genetic material inside.
previous studies have shown that hive is mainly used to protect the virus's genetic material.
the study, the researchers found that the shell appeared to play a key role in infecting cells with the virus.
when genetic and bio-chemical methods are used to destabilize the shell, HIV is unable to effectively replicate its genetic material.
further analysis, the researchers used frozen electron microscopes and molecular modeling techniques to visualize each shell protein on the virus's shell.
Through close observation, the researchers found that the virus shelling was carried out through a series of decomposition intermediates, and after 8 to 10 hours the viral nucleic acid chain was squeezed out of the lattice opening, and the virus casing remained essentially intact during the ERT reaction.
core of the image during virus replication.
(A) a fault slice of a fractured core observed after 8 to 10 hours under standard ERT conditions.
(B) shell lattice mapping and 3D arrangement chart This is the first study to directly prove that the shell is not only the "packaging" of the virus, but also plays a positive role in its infection process.
s different from what the textbook says," sundquist said.
our data show that viral shells play an active and indispensable role in supporting effective reversals.
" In summary, this study sheds new ground on the principles of HIV infection and helps explain why some hiv-related drugs are prominent in clinical trials, suggesting that HIV clospice may be an important breakthrough in improving the treatment of AIDS, a lifelong disease.
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