Efficacious control of cytomegalovirus infection after long-term depletion of CD8+ T lymphocytes

Although the relative contribution of different immune effector functions to clearing tissues of cytomegalovirus is controversial, the contribution of CD8+ T lymphocytes has generally been accepted as essential. In this report, we show that under certain conditions the CD8+ T-lymphocyte subset can be dispensable for clearance of cytomegalovirus. Mice depleted of the CD8+ T-lymphocyte subset eliminated infectious virus with a clearance kinetics similar to that of normal mice. Adoptive transfer studies revealed that the limitation of virus spread required the cooperation between the CD4+ subset and other cells. Comparison between protective functions generated in fully immunocompetent and in CD8- mice demonstrated that elimination of the CD8+ subset before infection altered the quality of the antiviral immune response. The compensatory protective activity gained by CD4+ cells in CD8- mice was absent in normal mice recovering from virus infection

Gamma interferon-dependent clearance of cytomegalovirus infection in salivary glands

Cytomegalovirus (CMV), similar to other members of the Herpesviridae family, can establish both persistent and latent infections. Each of the CMVs that are found in many animal species replicates in the salivary gland, and oral secretion represents a source of horizontal transmission. Locally restricted replication characterizes the immunocompetent individual, whereas in the immunocompromised host, protean disease manifestations occur due to virus dissemination. The virus is cleared by immune surveillance, and CD8+ T lymphocytes play a major role. Remarkably, certain cell types of salivary gland tissues are exempt from CD8+ T-lymphocyte control of murine CMV infection and require the activity of CD4+ T lymphocytes. The results presented here suggest that this activity is a function of Th1 cells. Neutralization of endogenous gamma interferon abrogated the antiviral activity of Th1 cells but not that of CD8+ T lymphocytes in other tissues. Neutralization of endogenous gamma interferon did not interfere with the induction of the cellular and humoral immune response but acted during the effector phase. Recombinant gamma interferon could not replace the function of Th1 cells in vivo and had limited direct antiviral activity in vitro. The results therefore suggest that gamma interferon represents one, but not the only, essential factor involved in salivary gland clearance, establishment of CMV latency, and, eventually, the control of horizontal transmission

Expression of the murine cytomegalovirus glycoprotein H by recombinant vaccinia virus

The sequence of the gene encoding glycoprotein H (gH) of murine cytomegalovirus (MCMV) strain Smith was determined and compared with the sequence of the gH of MCMV strain K181. Transcriptional analysis showed that gH is encoded by a large mRNA of 5.0 kb, which is synthesized late in infection. A recombinant vaccinia virus expressing the MCMV gH open reading frame was constructed (Vac-gH). Anti-MCMV serum precipitated a protein of 87K from Vac-gH-infected cells. Reactivity with a monoclonal antibody showed the identity of the MCMV gH with a 87K envelope glycoprotein described previously by Loh and Qualtiere. Immunization of mice with the Vac-gH recombinant gave rise to an anti-gH serum, which neutralized MCMV without complement in vitro

Late phase inhibition of murine cytomegalovirus replication by synergistic action of interferon-gamma and tumour necrosis factor

We have shown previously that the antiviral function of CD4+ T lymphocytes against murine cytomegalovirus (MCMV) is associated with the release of interferon- (IFN-). We now demonstrate that IFN- and tumour necrosis factor alpha (TNF-) display synergism in their antiviral activity. As little as 2 ng/ml of IFN- and TNF- reduced the virus yield by about three orders of magnitude. There was no effect on immediate early (IE) and early (E) gene expression as far as the candidate genes IE1, E1 and those encoding the major DNA-binding protein and the DNA polymerase were concerned. Late gene transcription, assayed by the candidate genes encoding glycoprotein B and the MCMV homologue of ICP 18.5, was blocked and MCMV DNA replication was found to be reduced but not halted. The most prominent finding of the cytokine effect, seen by electron microscopy, was an alteration of nucleocapsid formation. Altogether, the synergism is multifaceted and acts at more than one stage during viral morphogenesis. Because the cytokines clearly do not act at an early stage of infection we conclude that the mode of cytokine activity differs between alpha- and betaherpesviruses

Antibodies Are Not Essential for the Resolution of Primary Cytomegalovirus Infection but Limit Dissemination of Recurrent Virus

Virus shedding from the epithelial cells of the serous acini of salivary glands is a major source for the horizontal transmission of cytomegalovirus. These cells are, different to other tissues, exempt from CD8 T lymphocyte control. CD4 T lymphocytes are essential to terminate the productive infection. Here, we prove that T-B cooperation and the production of antibodies are not required for this process. For the infection with murine cytomegalovirus, mutant mice were used which do not produce antibodies because of a disrupted membrane exon of the immunoglobulin # chain gene. Also, in these mice the virus clearance from salivary glands is a function of CD4 T lymphocytes. However, these mice clear the virus and establish viral latency with a kinetics that is distinguishable from normal mice. Reactivation from virus latency is the only stage at which the absence of antibodies alters the phenotype of infection. In immunoglobulindeficient mice, virus recurrence results in higher virus titers. The adoptive serum transfer proved that antibody is the limited factor that prevents virus dissemination in the immunodeficient hos

Cytomegalovirus prevents antigen presentation by blocking the transport of peptide-loaded major histocompatibility complex class I molecules into the medial-Golgi compartment

Selective expression of murine cytomegalovirus (MCMV) immediate-early (IE) genes leads to the presentation by the major histocompatibility complex (MHC) class I molecule L a of a peptide derived from MCMV IE protein pp89 (Reddehase, M. J., J. B. Rothbard, and U. H. Koszinowski. 1989. Nature (Lond.). 337:651). Characterization of endogenous antigenic peptides identified the pp89 peptide as the nonapeptide msYPHFMFFNLt76 (del Val, M., H.-J. Schlicht, T. Ruppert, M. J. Reddehase, and U. H. Koszinowski. 1991. Cell. 66:1145). Subsequent expression of MCMV early genes prevents presentation of pp89 (del Val, M., K. Mfinch, M. J. Reddehase, and U. H. Koszinowski. 1989. Cell. 58:305). We report on the mechanism by which MCMV early genes interfere with antigen presentation. Expression of the IE promoter-driven bacterial gene lacZ by recombinant MCMV subjected antigen presentation of B-galactosidase to the same control and excluded antigen specificity. The La-dependent presence of naturally processed antigenic peptides also in nonpresenting cells located the inhibitory function subsequent to the step of antigen processing. The finding that during the E phase of MCMV gene expression the MHC class I heavy chain glycosylation remained in an Endo H-sensitive form suggested a block within the endoplasmic reticulum/c/s-Golgi compartment. The failure to present antigenic peptides was explained by a general retention of nascent assembled trimolecular MHC class I complexes. Accordingly, at later stages of infection a significant decrease of surface MHC class I expression was seen, whereas other membrane glycoproteins remained unaffected. Thus, MCMV E genes endow this virus with an effective immune evasion potential. These results also indicate that the formation of the trimolecular complex of MHC dass I heavy chain, ~2-microglobulin, and the finally trimmed peptide is completed before entering the medial-Golgi compartment

PENGARUH BANYAKNYA POPULASI MANUSIA RENTAN DALAM PENYEBARAN PENYAKIT MENULAR PADA PERHITUNGAN PREMI ASURANSI KESEHATAN

Polis asuransi akan bermanfaat jika dapat memberikan benefit yang sesuai dengan kebutuhan tertanggung. Dalam penentuan besaran benefit ini, terdapat beberapa faktor yang perlu diperhatikan apalagi jika benefit tersebut menutupi risiko karena pengaruh suatu penyakit, khususnya pada penyakit menular. Pada makalah ini, akan ditelaah pengaruh banyaknya populasi manusia rentan (susceptible) dengan menggunakan model Susceptible, Infected, Deceased, Recovered and Susceptible (SIDRS) dan menerapkan metode prinsip ekuivalensi fundamental pada perhitungan aktuaria dalam menentukan besaran premi. Diharapkan dengan memperhitungkan populasi manusia rentan ini, premi pada suatu polis asuransi dapat ditentukan dengan lebih akurat sehingga tidak merugikan perusahaan ketika memberikan benefit kepada pihak yang ditanggung. Dari hasil simulasi studi kasus, diperoleh kesimpulan bahwa perubahan populasi manusia rentan berbanding terbalik dengan perubahan besarnya premi, namun perubahan populasi manusia terinfeksi berbanding lurus dengan perubahan besarnya premi

Sportska natjecanja kao odraz političkih promjena u kontekstu sukoba Tito-Staljin (1948. – 1953.)

The Federal People’s Republic of Yugoslavia, headed by Josip Broz Tito, was the most radical of all the post-World War II communist countries in following the example of the Soviet Union. After gaining control over the country, Yugoslavian communists ushered in a single-party system, brutally dealing with any political opposition and members of the regimes defeated in the war. In addition, they nationalized the means of production, reformed the country’s agriculture, and implemented an economic programme based on heavy industry. The Communist Party of Yugoslavia (KPJ) also controlled the country’s cultural and scientific output, and in addition clashed with the most prominent religious leaders of the time. The importance of Yugoslavian communism within the European communist bloc was highlighted during the formation of the Information Bureau of the Communist and Workers' Parties (Cominform) in September of 1947, when Belgrade was selected as the seat of this forum. However, with the beginning of the Cold War, Tito’s aggressive foreign policy undermined Stalin’s efforts to avoid open conflict with the western powers. After the leadership of the KPJ ignored Stalin’s severe criticism of their policies, and refused to explain their positions on the matter before the Cominform, the forum passed a resolution in June of 1948 entitled “Concerning the Situation in the Communist Party of Yugoslavia”. This marked the beginning of military and economic pressure on Yugoslavia, which continued until Stalin’s death in March of 1953, and resulted in Yugoslavia turning to the West as well as the emergence of the so-called Third Way. The goal of this thesis is to determine whether, and in what way, the ideological and political conflict between Yugoslavia and the Soviet Union, along with the other members of the Cominform, influenced the interactions of Yugoslavian athletes and sports officials with their counterparts from those countries. Special attention was given to the available sources pertaining to the football match between Yugoslavia and the Soviet Union during the 1952 Helsinki Olympic Games. In addition to the changes in relations with the sports organizations of the Eastern bloc, the thesis gives a brief overview of the dynamics of the interactions of Yugoslavian athletes and sports teams with athletes and sports teams from the West, before and after the “Cominform Resolution”

Football and shaping national identity: the case of the Croatian national team and world cup in France

U sklopu ovog diplomskog rada teorijski se obrađuju fenomeni nacije, nacionalnog identiteta i nacionalnih simbola te se na primjeru Hrvatske nogometne reprezentacije i Svjetskog prvenstva u Francuskoj 1998. godine, kroz analizu diskursa, nastoji pokazati kako političke elite, posredstvom medija, koriste uspjeh na velikom sportskom natjecanju kako bi oblikovali i učvrstili osjećaj nacionalnog identiteta među pripadnicima pojedine nacije. Budući da je sport vrlo raširena i popularna društvena pojava koja je sastavni dio mnogih kultura, on je veoma pogodna arena za konstrukciju i rekonstrukciju identiteta, tj. mjesto gdje se na međunarodnoj razini proizvode nacionalne kulturne razlike, a što omogućava fokus sporta na simbole, natjecanje, pobjeđivanje i kolektivnu borbu.This thesis discusses the theory behind the phenomena of nation, national identity, and national symbols through the example of the Croatian national football team at the World Cup in France in 1998 by using discourse analysis and attempts to show how political elites, through the media, use success at large sporting events in order to shape and strengthen the sense of national identity among the people of a certain nation. Because sport is a widely spread and popular social phenomenon that is an integral part of many cultures, it is a very convenient arena for the construction and reconstruction of identity, i.e. a pace where national cultural differences are fashioned on an international level, which enables sports to focus on symbols, competition, winning, and collective struggle