I hypothesized that using only simple diffusion in the cytoplasm; viruses would take a longer time to reach the nucleus and be unable to properly proliferate. Rates of diffusion in the cytoplasm, movement along the microtubules, proliferation, and degradation were based on studies of adeno-associated virus AAV. I altered the level of infection number of viruses that pass the membrane , the initial viral location inside the cell membrane, the density of microtubules and the location of the MTOC.
I found that without microtubules, viruses effectively reach the nucleus at a slower time than with microtubules. Furthermore, without microtubules viruses reach the nucleus at all at a lesser probability. Infection Control. Section Navigation. Facebook Twitter LinkedIn Syndicate. How Do Infections Occur? Three things are necessary for an infection to occur: Source: Places where infectious agents germs live e.
Source Susceptible Person Transmission Source. People are one source of germs including: Patients Healthcare workers Visitors and household members People can be sick with symptoms of an infection or colonized with germs not have symptoms of an infection but able to pass the germs to others. Examples of environmental sources of germs include: Dry surfaces in patient care areas e. Susceptible Person. Certain medications used to treat medical conditions, such as antibiotics, steroids, and certain cancer fighting medications increase the risk of some types of infections.
The virus surfs along the fluid surface of the cell and eventually the viral fusion proteins bind to receptor molecules on the cell membrane 4. If only binding occurred, the two membranes would remain distinct. Fusion does not happen spontaneously because bilayers are stable. Fusion proteins do the work of prodding lipids from their initial bilayer configuration. These proteins cause discontinuities in the bilayers that induce the lipids of one membrane e. Fusion proceeds in two major steps Fig.
In the second step, the fusion proteins disrupt this single bilayer to create a pore that provides an aqueous pathway between the virus and the cell interior. It is through this fusion pore that the viral genome gains entry into a cell and begins infection. The steps of fusion. Virus binds to specific receptors each illustrated as a small cactus on a cell membrane.
Initially, four monolayers in blue separate the two interior aqueous compartments. After fusion peptides insert into the target membrane, monolayers that face each other merge and clear from the merged region.
The noncontacting monolayers bend into the cleared region and come into contact with each other, forming a new bilayer membrane known as a hemifusion diaphragm. At this point hemifusion , only two monolayers separate the compartments. The fusion protein acts as a nutcracker to force the formation of a pore within the hemifusion diaphragm.
This establishes continuity between the two aqueous compartments and fusion is complete. Hemifusion and pore formation appear to require comparable amounts of work, but the exact amount of energy needed for each step is not yet known 5.
These energetic details may be important because the more work required to achieve a step, the easier it may be to pharmacologically block that step. These energies are supplied by the viral fusion proteins, which are essentially molecular machines. Some of their parts move long distances during the steps of fusion. Fusion proteins can be thought of as a complex assembly of wrenches, pliers, drills, and other mechanical tools.
Because fusion is not spontaneous, discontinuities must be transiently created within the bilayer that allows water to reach the fatty, oily interior of the membrane. Even a short-lived exposure of a small patch of the fatty interior to water is energetically costly. Similarly, creating a pore in a hemifusion diaphragm requires exposure of the bilayer interior to water 6. In contrast, pore enlargement needs no such exposure. Nevertheless, pore enlargement requires the most amount of work in the fusion process.
Energy is also needed because of another fundamental property of bilayer membranes. Biological membranes have shapes that are determined by their precise lipids and the proteins associated with them 7. Work is required to force membranes out of their spontaneous shape, which is the shape of lowest energy.
The fusion pore that connects the virus and cell is roughly an hourglass shape 8. The wall of a fusion pore is a membrane with components that are a mixture of the two original membranes. An hourglass shape deviates significantly from the spontaneous shape of the initial membranes that constitute the pore. The greater the diameter of the pore, the greater is the area of the lining membrane, and so pore expansion is a highly energy consuming process.
In fact, it appears that more energy is required for pore expansion than for hemifusion or pore formation. All viral fusion proteins contain a greasy segment of amino acids, referred to as a fusion peptide or fusion loop. Soon after activation of the fusion protein, the fusion peptide inserts into the target membrane either plasma or endosomal. At this point, two extended segments of amino acids are anchored to the membranes: the fusion peptides in the target membrane and the membrane-spanning domains of the fusion proteins in the viral envelope Fig.
The fusion proteins continue to reconfigure, causing the two membrane-anchored domains to come toward each other. This pulls the viral envelope and cellular membrane closely together 9. The fusion proteins exert additional forces, but exactly what these forces are and how they promote fusion remains unknown. A virion engulfed into an endosome is like a Trojan horse, because the cell perceives the virus particle as food.
Fusion of viruses within endosomes depends critically on the acidic environment. By breaking molecular bonds, acid triggers the conformational changes in the fusion protein that lead to the sequential steps of membrane fusion.
The hemifusion diaphragm is a bilayer membrane that is unusual in that each of its lipid monolayers is derived from different membranes, and it does not contain any membrane-spanning proteins Several copies of the fusion protein within a virus are required to induce both hemifusion and pore formation.
During hemifusion, the proteins form a ring just outside the diaphragm and act cooperatively to create stresses that lead to a local rupture in the diaphragm, thereby creating the initial fusion pore.
The universality of this mechanism is remarkable when one considers that the primary amino acid sequences and structures of fusion proteins are quite diverse. Influenza, HIV, and Ebola are enveloped viruses of significant public health concern.
Viruses can mutate and combine with one another. The most important ones to humans are the ones that infect us. Some families of viruses, such as herpes viruses, can stay dormant in the body for long periods of time without causing negative effects. How much harm a virus or other pathogen can do is often described as its virulence.
In evolutionary terms, there is often a trade-off for a virus between replicating and doing harm to the host. A virus that replicates like crazy and kills its host very quickly may not have an opportunity to spread to a new host.
On the other hand, a virus that replicates slowly and causes little harm may have plenty of time to spread. Once a person is infected with a virus, their body becomes a reservoir of virus particles which can be released in bodily fluids — such as by coughing and sneezing — or by shedding skin or in some cases even touching surfaces.
0コメント