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At least 19 recordsLinked to original sources
PubMed1977

Prolongation of herpes simplex virus latency in cultured human cells by temperature elevation.

Treatment of herpes simplex virus type 2 (HSV-2)-infected human fibroblast cells with cytosine arabinoside (ara-C) at 25 microgram/ml resulted in complete inhibition of virus replication. Removal of ara-C after 7 days of treatment ultimately resulted in renewed virus replication, but after a delay of at least 5 days. If however, the temperature was elevated from 37 degrees C to 39.5 to 40 degrees C at the time of ara-C reversal, infectious HSV-2 did not reappear. As long as the cultures were maintained at 39.5 to 40 degrees C (up to at least 128 days), HSV-2 was latent and infectious virus was undetectable. If the temperature was reduced to 37 degrees C at any time during the latent period, infectious virus was always reactivated, but only after a period of incubation at 37 degrees C of a least 11 days. Infectious-center assays performed with latent cultures indicated that only a very small fraction of cells could reactivate virus. The infectious-center titer did not show significant changes during much of the period of latency. This seemed to argue against the possibility that the latent cultures were synthesizing very small amounts of infectious virus. Additional studies were aimed at determining the minimum incubation period at 37 degrees C required to reactivate infectious HSV-2. Latent cultures reduced from 39.5 to 40 degrees C to 37 degrees C for less than 96 h did not yield infectious HSV-2, but those incubated at 37 degrees C for 96 h or more did.

Culture Techniques↗
PubMed1978

Herpes simplex virus latency in patients with multiple sclerosis, lymphoma and normal humans.

Herpes simplex virus (HSV) was isolated from the trigeminal ganglia (TG) of 12 cadavers (10 traumatic deaths, one lymphoma and one multiple sclerosis). The cadaver with multiple sclerosis showed large bilateral trigeminal nerve root entry zone areas of demyelination. It is hypothesized that HSV is capable of migrating to the trigeminal nerve root entry zone and initiating demyelinating disease.

Adolescent↗
PubMed1975

Hazards from simian herpes viruses: reactivation of skin lesions with virus shedding.

A new simian herpes virus with biological properties similar to herpes simplex and to simian "B" virus has been used as a model system for studying virus latency in dorsal root spinal sensory ganglia. Following intradermal injection, virus is present in the skin lesions and corresponding ganglia only, during the acute stage of the disease. By organ-culture techniques, latent virus was rescued from ganglia up to 2 years later. No latent virus was ever found in skin organ cultures of the primary site. Treatment with cortisone up to 18 months later reactivated virus latent in the ganglia, and virus returned to the skin where it produced small but typical herpes lesions which shed virus. Reactivation of Herpesvirus tamarinus was achieved after 28 months. This is believed to be the first report of a model system for the study of herpes latency in which skin lesions are found to recur, and provides an opportunity for more detailed investigations of the mechanisms of virus latency in man. The presumption that reactivation of skin lesions will also be possible in rhesus monkeys seropositive for "B" virus points to a possibly grave and largely unsuspected hazard for those engaged in primate research.

Animals↗
PubMed1979

Latent herpes simplex virus infections in sensory ganglia of hairless mice prevented by acycloguanosine.

Acycloguanosine (ACG) was able to prevent the fatal outcome of herpes simplex virus-induced skin infections of the lumbosacral or orofacila area in hairless mice. Topical ACG treatment was more effective than systemic treatment in preventing the evolution of skin lesions. Acute ganglionic infections in the trigeminal ganglia were prevented by ACG, and latent ganglionic infections did not become established when the ACG treatment was initiated 3 h after infection. Serum antibody titers were, on the average, eight times higher in mice which developed latent ganglionic infections after ACG treatment than in mice without evidence of herpes simplex virus latency in ganglia. Reinoculation of ACG-treated mice at a site different from that of the primary inoculation did not lead to the establishment of a second latent infection with the homologous virus type when a latent infection was already present. In mice without evidence of latent infection after the primary inoculation, a latent infection at the site of reinoculation became established in 25% of the animals.

Animals↗
PubMed1976

Pathogenesis of cytomegalovirus infection. Distribution of viral products, immune complexes and autoimmunity during latent murine infection.

During studies on the mechanisms of virus latency, reactivation and resultant tissue injury in mice infected with murine cytomegalovirus (MCMV) in utero or at birth, we found the occurrence of three distinct pathological groups. In the first group, mice died within 4 weeks of exposure to virus and showed evidence of tissue injury due to MCMV in multiple tissues and organs of the body. The second group consisted of mice which survived the initial infection and was composed of a minority (about 25%) which shed virus (chronically infected). The third group (about 75%) consisted of mice in which shedding of virus could not be detected (latently infected). Study of the latter group indicated that virus was not detected in brain, thymus, liver, kidneys, urine or serum by co-cultivation techniques or by cellular DNA-MCMV DNA hybridization. In contrast, virus could be activated from spleen cells by co-cultivation with allogenic but not syngeneic feeder cells and MCMV-DNA was detected in amounts equivalent to 3 to 4 virus genomes per 100 spleen cells. In both the latently infected and chronically infected mice, in all strains studied evidence of virus-antivirus immune complex deposits in the renal glomeruli occurred. Only one of the six infected strains (C57 Br/cdJ) studied showed manifestations of autoimmune disease with the formation of antibodies to nuclear antigens, DNA and soluble nucleoprotein.

Animals↗
PubMed1979

Herpes simplex virus: benefit versus risk factors in immunization.

Vaccines developed against herpes simplex viruses (HSV) should be effective in two respects: (i) they should prevent primary infections and virus latency and (ii) if applied to individuals with recurrent herpetic lesions they should reduce the number of recurrences or at least mitigate the symptoms. The efficiency of vaccines which are presently available will be reviewed. Problems associated with the possible use of live attenuated or inactivated HSV vaccines will be discussed. Comparative aspects to existing vaccines against other herpes group viruses will be stressed.

Animals↗
PubMed1979

Pathogenesis of reactivated latent murine cytomegalovirus infection.

Sixteen weeks after inoculation, murine cytomegalovirus (MCMV) can no longer be detected in the tissues of mice. However, a 2-week course of immunosuppression with antilymphocyte serum and cortisone acetate results in reactivation and dissemination of the latent virus in all animals. In this study of reactivation, MCMV was first detected in the liver, usually during the first week of immunosuppression, and virus replication was shown to be restricted to hepatocytes. Subsequently, a viremia occurred, with spread of infection to other organs. The highest titers of virus were reached in salivary glands in which replication occurred in serous acinar cells. In the lung, virus-specific abnormalities were difficult to detect because of superimposed bacterial and fungal infections. However, interstitial pneumonitis could be produced when cortisone acetate was deleted from the immunosuppressive regimen. Although the site of virus latency has not been defined, this model system will be useful for study of reactivation of latent cytomegalovirus infection.

Animals↗
PubMed1979

Effect of pyran on latency after herpes simplex virus infections.

The immunomodulator pyran protected mice against both herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2) infections. In infections of the lip with HSV-1, prophylactic administration of pyran reduced the severity of the herpetic lesions and enhanced their resolution, but did not decrease the high incidence of development of latent HSV-1 infection of the trigeminal ganglia. In vaginal infections with HSV-2, prophylactic administration of pyran either systemically or locally reduced mortality, reduced the incidence of mice with vaginal HSV-2 infection, and did not alter the low incidence of latent infection of the spinal dorsal root ganglia. Pyran treatment before systemic herpetic infection after intravenous inoculation of HSV-2 also reduced mortality and virus replication, as evidenced by a decreased antibody response in the survivors, and it either reduced latent infection in the spinal dorsal root ganglia or did not predispose mice to latent infection. Treatment with the immunomodulator appeared to inhibit or reduce HSV infection early in viral pathogenesis in all three model systems, producing protection from clinical disease and resulting in less virus to induce a systemic antibody response, with either a reduction in latent virus infection or no enhancement of development of latency. In all of the HSV models, the development of latent herpetic infection was closely correlated with sufficient virus replication early in the infection to induce a systemic neutralizing-antibody response.

Animals↗
PubMed1975

Immunological basis for latency, recurrences and putative oncogenicity of herpes simplex virus.

The development of latency and recurrent infection after primary herpes simplex virus (H.S.V.) infection can be interpreted in terms of cell-mediated and antibody responses to virus-specific antigens and Fc receptors on the surface of the infected cells. Primary infection will induce immune responses to the virus, and antibody and cell-dependent cytotoxic mechanisms will kill most of the virus and virus-infected cells which are accessible to killer cells. H.S.V. will be sequestrated to the nerves and will migrate centripetally along the axons to the trigeminal or sensory ganglia. Latency in the trigeminal ganglion may be mediated by IgG antibodies binding to both H.S.V. antigens and Fc receptors. Derepression of the viral genome may be induced by factors which weaken the binding of antibodies to the antigen and Fc receptor; the virus will replicate and migrate centrifugally along the axon, to be shed at the nerve endings. In the presence of some defect in T lymphocytes, acting at the neuroepithelial junction, a recurrent herpetic lesion will be precipitated. There is some evidence that H.S.V. may be associated with squamous-cell carcinoma, and it is postulated that the enhanced cell-mediated and antibody responses to H.S.V. may destroy cells containing the viral genome but allow the emergence of an oncogenic genome. Double binding of the Fc receptor and H.S.V. antigen by IgG antibodies or immune complexes on the surface of carcinoma cells may prevent killing and allow these cells to proliferate into invasive tumours.

Antibodies, Viral↗
PubMed1979

[Evolution of viral diseases (author's transl)].

Biological characteristics of viruses determine their distribution in men and animals as well as their means of surviving or persisting. Taking measles as an example, we show that we are dealing with a recent phenomenon in evolution--as opposed, for instance, to those infections due to arboviruses (eg yellow fever) common in tropical regions. Survival rates are lower for highly virulent viruses (myxomatosis). Antigenmodification (influenza) or latency (herpes virus infections) allow the virus repeatedly to escape the body's immune system. The distribution and clinical appearance of the infections are influenced by environmental and particularly iatrogenic impact. Complete extirpation of infections will not be possible, only their manifestations will undergo continuous change.

Animals↗
PubMed2025

A targeted CRISPR screen identifies ETS1 as a regulator of HIV-1 latency.

Human Immunodeficiency virus (HIV) infection is regulated by a wide array of host cell factors that combine to influence viral transcription and latency. To understand the complex relationship between the host cell and HIV-1 latency, we performed a lentiviral CRISPR screen that targeted a set of host cell genes whose expression or activity correlates with HIV-1 expression. We further investigated one of the identified factors - the transcription factor ETS1, and found that it is required for maintenance of HIV-1 latency in both latently infected cell lines and in a primary CD4 T cell latency model. Interestingly, ETS1 played divergent roles in actively infected and latently infected CD4 T cells, with knockout of ETS1 leading to reduced HIV-1 expression in actively infected cells, but increased HIV-1 expression in latently infected cells, indicating that ETS1 can play both a positive and negative role in HIV-1 expression. CRISPR/Cas9 knockout of ETS1 in CD4 T cells from ART-suppressed people with HIV-1 (PWH) confirmed that ETS1 maintains transcriptional repression of the clinical HIV-1 reservoir. Transcriptomic profiling of ETS1-depleted cells from PWH identified a set of host cell pathways involved in viral transcription that are controlled by ETS1 in resting CD4 T cells. In particular, we observed that ETS1 knockout increased expression of the long non-coding RNA MALAT1 that has been previously identified as a positive regulator of HIV-1 expression. Furthermore, the impact of ETS1 depletion on HIV-1 expression in latently infected cells was partially dependent on MALAT1. Additionally, we demonstrate that ETS1 knockout resulted in enhanced abundance of activating modifications (H3K9Ac, H3K27Ac, H3K4me3) on histones located at the HIV-1 long terminal repeat (LTR), indicating that ETS1 regulates the activity of chromatin-targeting complexes at the HIV-1 LTR. Overall, these data demonstrate that ETS1 is an important regulator of HIV-1 latency that impacts HIV-1 expression through repressing MALAT1 expression and by regulating modification of proviral histones.

Proto-Oncogene Protein c-ets-1↗
PubMed1975

Effect of host age, virus dose, and route of inoculation on tumor incidence, latency, and morphology in Syrian hamsters inoculated intravenously with oncogenic DNA simian virus 40.

Three-week-old to 12-month-old male Syrian hamsters were inoculated iv with 10(8.5) median tissue culture infective dose of simian virus 40 (SV40). Three-week-old hamsters were similarly inoculated with aliquots of SV40 of progressively decreasing titers. The tumor incidence and, to a lesser extent, the tumor latency were directly dependent on the age of the animals at the time of virus exposure and on the dose of the virus. However, this age-dose dependence was not of the magnitude usually observed in hamsters inoculated with SV40 sc or im. Moreover, the wide morphologic spectrum of neoplasms induced, i.e., lymphosarcoma, reticulum cell sarcoma, and osteogenic sarcoma, by iv route of inoculation, contrasted sharply with the anaplastic and spindle-cell sarcomas which were the only types of malignant tumors resulting when other routes were used.

Age Factors↗
PubMed1979

Acylovir in oral and ganglionic herpes simplex virus infections.

The local and trigeminal ganglionic therapeutic efficacy of two topical and systemic antiviral drugs was studied in mouse lips inoculated with herpes simplex virus type 1 after thermal injury. Application of topical 3% acylovir (acycloguanosine) ointment three times daily for four days completely blocked the replication of virus in the lips, and the healing process was greatly accelerated compared with that in placebo-treated infected controls. However, neither the healing process nor the viral replication was influenced by similar therapy with 3% vidarabine ointment. When given systemically for four days, starting one day after inoculation, acyclovir (40-60 mg/kg per day) and vidarabine (50 mg/kg per day) significantly reduced the clinical manifestations on the lips and viral titers of cultures obtained from the lips. Establishment of viral latency in the trigeminal ganglion was significnatly inhibited by systemic acyclovir (60 mg/kg per day), whereas systemic vidarabine (50 mg/kg per day) was ineffective. These data suggest that acyclovir may be one of the most promising antiviral agents for the management of oral herpes viral infections and trigeminal ganglionic latency of virus as demonstrated in the mouse model.

Animals↗
PubMed2025

Unidirectional recruitment between MeCP2 and KSHV-encoded LANA revealed by CRISPR/Cas9 recruitment assay.

Kaposi's sarcoma-associated herpesvirus (KSHV, HHV-8) is associated with several human malignancies. During latency, the viral genomes reside in the nucleus of infected cells as large non-integrated plasmids, known as episomes. To ensure episome maintenance, the latency protein LANA tethers the viral episomes to the cell chromosomes during cell division. Directional recruitment of protein complexes is critical for the proper function of many nuclear processes. To test for recruitment directionality between LANA and cellular proteins, we directed LANA via catalytically inactive Cas9 (dCas9) to a repeat sequence to obtain easily detectable dots. Then, the recruitment of nuclear proteins to these dots can be evaluated. We termed this assay CRISPR-PITA for Protein Interaction and Telomere Recruitment Assay. Using this protein recruitment assay, we found that LANA recruits its known interactors ORC2 and SIN3A. Interestingly, LANA was unable to recruit MeCP2, but MeCP2 recruited LANA. Both LANA and histone deacetylase 1 (HDAC1) interact with the transcriptional-repression domain (TRD) and the methyl-CpG-binding domain (MBD) of MeCP2. Similar to LANA, HDAC1 was unable to recruit MeCP2. While heterochromatin protein 1 (HP1), which interacts with the N-terminal of MeCP2, can recruit MeCP2. We propose that available interacting domains force this recruitment directionality. We hypothesized that the tandem repeats in the SunTag may force MeCP2 dimerization and mimic the form of DNA-bound MeCP2. Indeed, providing only the tandem epitopes of SunTag allows LANA to recruit MeCP2 in infected cells. Therefore, CRISPR-PITA revealed the rules of unidirectional recruitment and allowed us to break this directionality.

Humans↗