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HSV takes advantage of the neuronal stress response to enter into a silent, latent state. To assist in the execution of this plan, HSV evolved a DNA sequence that allows itself to be suppressed in neurons and a mechanism to maintain an equilibrium between total suppression and potential to exit from the latent state.

translocated from satellite cells

The fundamental question is the identity of the mechanism by which a vigorously replicating virus, on entry into the body, is silenced in neurons harboring latent virus.

Thus, VP16, a virion protein brought into the cells during infection, recruits several cellular proteins, including LSD1, to derepress α gene promoters

In some neurons, the virus establishes a latent, silent state. In other neurons, the virus replicates, and it is most likely that the virus in these neurons is transmitted and replicates in other ganglionic cells.

Finally, in contrast to the events following entry of virus after retrograde transport from the periphery, the data suggest that reactivation does not trigger a stress response that leads to activation of REST

Thus, VP16, a virion protein brought into the cells during infection, recruits several cellular proteins, including LSD1, to derepress α gene promoters. One α gene product, infected cell protein 0 (ICP0), derepresses β and γ1 genes. Ultimately, the onset of viral DNA synthesis enables the expression of very late, or γ2, genes (4).

In contrast, simultaneous expression of all viral genes during reactivation from latency is likely to minimize yield, but the mission of the virus is to assemble enough viruses to reach the portal of egress from the body (e.g., mouth, genitals) rather than to overwhelm the host with infectious virus.

Between 5 and 24 h after excision, mRNAs representative of all viral gene kinetic groups increase 100-fold in amount. Viral DNA also increases in amount, indicating that viral proteins are made. At the same time, viral LAT and miRNA concentrations decrease at least 10-fold (34). It is convenient to define the initial phase lasting no more than 5 h as the preactivation phase and the remaining time interval as the activation phase.

The same concentration of HDAC inhibitor was ineffective in inducing the reactivation of R111 recombinant virus in ganglionic organ cultures maintained in medium containing anti-NGF antibody.

Foreign immunogens or peptides can be displayed on the envelope of AcMNPV by fusion with the baculovirus major envelope protein gp64

Baculoviruses have strong adjuvant activity to promote humoral and cellular immune responses against coadministered antigens, activate dendritic cells maturation, induce the production of cytokines, chemokines, and type I IFNs

There are two influenza vaccine approaches licensed in the US; the inactivated, split vaccine and the live-attenuated virus vaccine. Inactivated vaccines can efficiently induce humoral immune responses but generally only poor cellular immune responses.

Therefore, influenza HA can be displayed on the surface of baculovirus

virus-like particle (VLP)

Even though cellular immune responses cannot confer sterilizing immunity, they are able to reduce the severity of infection and lower morbidity and mortality rates [47], and antigen-specific memory T cells are able to rapidly respond to a secondary virus infection [45]. Furthermore, cellular immune responses to the conserved epitopes contained in vaccines may provide cross-protective immunity against different subtypes of influenza virus infection

To confirm that each HA was incorporated on the envelope of baculoviruses, supernatants from infected Sf9 cells were used to perform hemagglutination assay

Most BV display strategies rely on gp64 protein which is the major envelope protein of baculovirus.

Manufacturers for the most part still make flu vaccines the way they did in World War II: in chicken eggs.

Within the VF, viral core particles transcribe and release viral mRNAs that possess a dimethylated cap 1 structure at the 5′ terminus but lack a poly(A) tail (19).

Consistent with our findings, the authors noted that the rough endoplasmic reticulum (RER) made numerous contacts with VF, which they suggested may indicate a role for RER in the transport of newly synthesized viral proteins to the VF, as is the case for rubella virus (64).

To address this, we monitored protein expression levels of eIF4E, eIF4A1, and eIF4G over the course of an infection. As others have found (39), we were unable to detect any difference in the levels of total protein in mock versus infected cells from 0 to 20 h p.i. (Fig. 3C and data not shown). Together, these data suggest that cellular translation proteins are redistributed to the VF.

Most reovirus strains form filamentous VF through an association with stabilized microtubules. However, the T3D strain used in these experiments contains a temperature-sensitive mutation in the viral protein μ2 that prevents this association, resulting in the production of globular VF at 37°C (27, 28). Therefore, to evaluate if PMY labeling occurs within filamentous viral factories, we infected cells with the serotype 1 Lang (T1L) strain. As we found for T3D-infected cells, the PMY labeling localized to T1L VF at 18 h postinfection

It was unclear if this was a result of increased expression levels or as a consequence of redistribution of the proteins to the factories. To address this, we monitored protein expression levels of eIF4E, eIF4A1, and eIF4G over the course of an infection. As others have found (39), we were unable to detect any difference in the levels of total protein in mock versus infected cells from 0 to 20 h p.i. (Fig. 3C and data not shown). Together, these data suggest that cellular translation proteins are redistributed to the VF.

Our finding that σNS interacts with eIF3A and pS6R suggests that translational machinery is recruited to the factory by viral proteins. This is consistent with the finding of others that σNS cosediments with 40S and 60S ribosomes (62) and suggests that σNS is directly involved in viral translation.

FIG 3  Cellular translation initiation factors colocalize to viral factories. (A, B) CV-1 cells were infected with T3D or T1L at an MOI of 1. At 18 h p.i., RPM-labeled cells were coimmunostained for μNS and eIF4E (A) or eIF3A (B). Scale bars, 10 µm. (C) CV-1 cells were infected with T3D, MOI of 3, for the times indicated. Protein levels were assessed by immunoblotting. M = mock.