Horizontal and vertical transmission of viruses in the honey bee, Apis mellifera

The most crucial stage in the dynamics of virus infections is the mode of virus transmission. In general, transmission of viruses can occur through two pathways: horizontal and vertical transmission. In horizontal transmission, viruses are transmitted among individuals of the same generation, while vertical transmission occurs from mothers to their offspring. Because of its highly organized social structure and crowded population density, the honey bee colony represents a risky environment for the spread of disease infection. Like other plant and animal viruses, bee viruses use different survival strategies, including utilization of both horizontal and vertical routes, to transmit and maintain levels in a host population. In this review, we explore the current knowledge about the honey bee viruses and transmission routes of bee viruses. In addition, different transmission strategies on the persistence and dynamics of host-pathogen interactions are also discussed.     

Immune tolerance split between hepatitis B virus precore and core proteins

The function of the hepatitis B virus (HBV) precore or HBeAg is largely unknown because it is not required for viral assembly, infection, or replication. However, the HBeAg does appear to play a role in viral persistence. It has been suggested that the HBeAg may promote HBV chronicity by functioning as an immunoregulatory protein. As a model of chronic HBeAg exposure and to examine the tolerogenic potential of the HBV precore and core (HBcAg) proteins, HBc/HBeAg-transgenic (Tg) mice crossed with T cell receptor (TCR)-Tg mice expressing receptors for the HBc/HBeAgs (i.e., TCR-antigen double-Tg pairs) were produced. This study revealed three phenotypes of HBe/HBcAg-specific T-cell tolerance: (i) profound T-cell tolerance most likely mediated by clonal deletion, (ii) T-cell clonal ignorance, and (iii) nondeletional T-cell tolerance mediated by clonal anergy and dependent on the structure, location, and concentration of the tolerogen. The secreted HBeAg is significantly more efficient than the intracellular HBcAg at eliciting T-cell tolerance. The split T-cell tolerance between the HBeAg and the HBcAg and the clonal heterogeneity of HBc/HBeAg-specific T-cell tolerance may have significant implications for natural HBV infection and especially for precore-negative chronic hepatitis.     

Characteristics of the distribution of the markers of hepatitis B vir us infection among the healthy population of the Tadzhik SSR and Azerbaijan SSR

A total of 708 healthy persons in Tajikistan and 576 healthy persons in Azerbaijan, these groups comprising persons of both sexes and different age groups, were examined by the method of double gel immunodiffusion (the gel precipitation test) and by the passive hemagglutination test for the presence of the markers of hepatitis B virus (HBV) infection (HBsAg and HBeAg) and antibodies to them. This investigation showed that, in accordance with the level of hepatitis B morbidity, HBsAg was significantly more often detected among the population in Tajikistan (7.2%) than in Azerbaijan (2.8%). In both republics HBV carriers occurred most frequently among children aged 1-4 years (4.0% in Azerbaijan and 13.9% in Tajikistan), and among men more frequently than among women. In accordance with different intensity of the spread of HBV infection in the territories under comparison, differences in the age structure of the immune population were noted: in Tajikistan the formation of the immune layer occurred most frequently among younger age groups and in Azerbaijan, among senior adult age groups. The presence of a considerable percentage of persons with HBe-antigenemia (14.3-14.9% as determined by the gel precipitation test) among HBV carriers, observed in Tajikistan and in Azerbaijan, indicates that some of them have undetected chronic hepatitis B.     

Hepatitis B e Antigen Status and Hepatitis B DNA Levels in Women of Childbearing Age with Chronic Hepatitis B Infection Screening for Clinical Trials

Background

Perinatal or mother-to-child transmission of hepatitis B virus (HBV) results in a high frequency of chronic infection. Risk of mother-to-child transmission is associated with maternal viral factors including hepatitis B e antigen (HBeAg) positivity and viral load.

Aim

To investigate associations between age, HBeAg status, HBV DNA levels and genotype in female patients screened for inclusion into two contemporary, randomized HBV trials.

Methods

Retrospective analyses focused on differences between women of childbearing age (≤44 years) and older women. Female patients (N = 355; 18–69 years) were included in the analysis: 41.7% of patients were Asian. In total, 44.4% were HBeAg-positive.

Results

Significantly more women aged ≤44 years were HBeAg-positive compared to women ≥45 years (57.2% versus 27.5%, respectively, p<0.0001), this proportion declined with increasing age. Younger women were significantly more likely to have high HBV viral load (HBV DNA>10⁸ copies mL: ≤44 years 46.0% vs ≥45 years 25.5%, respectively; p<0.0001), and this declined with increasing age. HBeAg positivity was slightly higher in Asian women, associated with a higher proportion of HBV genotypes B and C in this population. There was no obvious relationship between genotype and viral load.

Conclusions

Women of childbearing age with CHB are more likely to have high HBV viral load and HBeAg positivity than older women; this likelihood decreases with age. Maternal serological and virological status should therefore be established early in pregnancy, taking into account age and genotype, and a risk-reducing strategy implemented in any patient who is HBeAg positive and has a high viral load.     

A Multi-scale Analysis of Influenza A Virus Fitness Trade-offs due to Temperature-dependent Virus Persistence

Successful replication within an infected host and successful transmission between hosts are key to the continued spread of most pathogens. Competing selection pressures exerted at these different scales can lead to evolutionary trade-offs between the determinants of fitness within and between hosts. Here, we examine such a trade-off in the context of influenza A viruses and the differential pressures exerted by temperature-dependent virus persistence. For a panel of avian influenza A virus strains, we find evidence for a trade-off between the persistence at high versus low temperatures. Combining a within-host model of influenza infection dynamics with a between-host transmission model, we study how such a trade-off affects virus fitness on the host population level. We show that conclusions regarding overall fitness are affected by the type of link assumed between the within- and between-host levels and the main route of transmission (direct or environmental). The relative importance of virulence and immune response mediated virus clearance are also found to influence the fitness impacts of virus persistence at low versus high temperatures. Based on our results, we predict that if transmission occurs mainly directly and scales linearly with virus load, and virulence or immune responses are negligible, the evolutionary pressure for influenza viruses to evolve toward good persistence at high within-host temperatures dominates. For all other scenarios, influenza viruses with good environmental persistence at low temperatures seem to be favored.     

Human hepatitis B viral e antigen and its precursor P20 inhibit T lymphocyte proliferation

The hepatitis B virus (HBV) Precore protein is processed through the secretory pathway directly as HBeAg or with the generation of an intermediate (P20). Precore gene has been shown to be implicated in viral persistence, but the functions of HBeAg and its precursors have not been fully elucidated. We show that the secreted proteins HBeAg and P20 interact with T cell surface and alter Kit-225 and primary T cells proliferation, a process which may facilitate the establishment of HBV persistence. Our data indicate that the N-terminal end of Precore is important for these inhibitory effects and exclude that they are dependent on the association of HBeAg and P20 with two characterized cell surface ligands, the Interleukin-1 Receptor Accessory Protein and gC1qR (present study).     

Low frequency of precore mutants in anti-hepatitis B e antigen positive subjects with chronic hepatitis B virus infection in Chennai, Southern India

The natural course of chronic hepatitis B (CH-B) virus infection is reportedly variable, and the long-term outcomes in hepatitis B e antigen (HBeAg)-negative chronic hepatitis B infection are distinct from HBeAg-positive chronic hepatitis. However, the molecular virological factors that contribute to the progression of liver disease in the south Indian setting remain largely unclear. We prospectively studied 679 consecutive patients for HBsAg, HBeAg, anti-HBeAg, and HBV DNA by qualitative PCR. Randomly selected samples were subjected to bidirectional sequencing to reveal core/precore variants. Of the total 679 chronic HBV cases investigated, 23% (154/679) were replicative HBV carriers. Furthermore, amongst the 560 HBV DNA samples analyzed, 26% (146/560) were viremic. Among the 154 HBeAg positive cases, HBV DNA was positive in 118 cases (77%), significantly (p<0.001) higher than the anti-HBe positive (7%) (28/406) cases. Significant increase in liver disease (p<0.01) with ALT enzyme elevation (p<0.001) was observed in both HBe and anti-HBe viremic cases. Interestingly, low frequencies of mutations were seen in the precore region of the HBV strains studied. HBV precore and core promoter variants were less often detected in subjects with "e" negative chronic HBV infection and, therefore, may not have a prognostic role in determining liver disease sequelae in this part of tropical India.     

Seroprevalence of Hepatitis B virus infection among an Afro-descendant community in Brazil

Furnas dos Dionísios is an Afro-Brazilian black community whose descendants were mainly fugitive slaves that established themselves in the State of Mato Grosso do Sul (MS), Brazil. The population is comprised mainly of low socioeconomic individuals who are engaged in agricultural activities. The objective of this study was to investigate the prevalence of hepatitis B (HB) and its correlation with epidemiological data obtained from the community. The studied population totaled 260 individuals with ages varying from 1 to 79 years (median 20). One hundred thirty-three (51.2%) were females and 127 (48.8%) were males. A high prevalence for anti-HBc was observed (42.7%), with present infection detected in 9.2% of the subjects who were also HB surface antigens (HBs Ag) positive; 27.3% were anti-HBc and anti-HBs reactive, and 6.2% had anti-HBc as only marker. The prevalence for anti-HBc was proportional to age, reaching its highest peak in age categories greater than 50. No serological marker was detected in children under the age of 2 years, however anti-HBc was present in 12 subjects with ages between 2 and 14 years, of these 8 (7.4%) were HBsAg positive. Among individuals over the age of 15 years, 99 were anti-HBc reactive, of these 16 (10.5%) were also HBsAg positive, thus suggesting an increased prevalence of HBV carriers among children and adolescents. The risk factors observed in this community that were significantly associated with anti-HBc positivity were age (over 20 years) and having an anti-HBc positive mother. Both HBeAg and anti-HBe were detected in 44.4% of the samples tested. HBsAg subtypes found in the studied population were adw2 (77.7%) and ayw2 (23.3%). While intrafamilial transmission was most likely responsible for HBV infection among children, other routes such as sexual contact might be considered for individuals with ages over 15 years.     

Quantifying transmission dynamics of acute hepatitis C virus infections in a heterogeneous population using sequence data

Opioid substitution and syringes exchange programs have drastically reduced hepatitis C virus (HCV) spread in France but HCV sexual transmission in men having sex with men (MSM) has recently arisen as a significant public health concern. The fact that the virus is transmitting in a heterogeneous population, with different transmission routes, makes prevalence and incidence rates poorly informative. However, additional insights can be gained by analyzing virus phylogenies inferred from dated genetic sequence data. By combining a phylodynamics approach based on Approximate Bayesian Computation (ABC) and an original transmission model, we estimate key epidemiological parameters of an ongoing HCV epidemic among MSMs in Lyon (France). We show that this new epidemic is largely independent of the previously observed non-MSM HCV epidemics and that its doubling time is ten times lower (0.44 years versus 4.37 years). These results have practical implications for HCV control and illustrate the additional information provided by virus genomics in public health.     

沈阳市居民乙肝感染状况调查

对不同性别、年龄的沈阳市居民乙型肝炎病毒血清标志物进行检测,分析HBV感染状况。采集3 780名健康体检者血清标本检测乙肝5项、ALT和TBIL,统计分析后的结果显示:乙肝感染率为3.28%,不同性别间结果无明显差异(P>0.05),但不同年龄组间乙肝感染率有显著差异(P<0.01),41～50岁年龄组感染率是6.23%,30岁以下和50岁以上感染率较低,分别为2.94%和1.84%;1、4、5感染模式占总感染例数的69.4%,HBV感染者中ALT或TBIL单项升高及二者均升高者占22.6%。沈阳市居民乙肝感染率低于全国平均水平,慢性乙肝感染较多,肝功能与乙肝感染病程不呈平行关系,疫苗接种可有效预防乙肝感染。     

Pegylated interferon alpha-2a (40 kDa) in the treatment of chronic hepatitis B

Chronic hepatitis B virus (HBV) is a serious and life-threatening disease afflicting 350 million of the world's population. So far, current monotherapy with conventional interferon-alpha, lamivudine, and adefovir dipivoxil remains unsatisfactory. In addition, the use of conventional interferon-alpha needs to be administered subcutaneously daily or thrice weekly and is associated with frequent adverse events. Although nucleoside-nucleotide analogs such as lamivudine and adefovir dipivoxil are well tolerated and can normalize serum alanine aminotransaminase rapidly, 1-year therapy with either lamivudine or adefovir dipivoxil results in low hepatitis B e antigen (HBeAg) seroconversion rates. In HBeAg negative patients, most of the patients would relapse after lamivudine has been discontinued. Pegylated interferon alpha-2a, an immunomodulatory agent, is a new drug that has just completed phase III clinical trials for the treatment of both HBeAg positive and HBeAg negative chronic HBV infection. The advantage of pegylated interferon alpha-2a in achieving sustained virological response over nucleoside-nucleotide analogs is particularly obvious in the HBeAg negative group. In both of these phase III studies, sustained off-treatment response is superior to the use of lamivudine. These recent data put pegylated interferon alpha-2a as the first choice of anti-HBV therapy, especially in young and motivated patients with chronic HBV infection.     

Asymptomatic hepatitis among the Asmat

An investigation for HAV and HBV markers of infection was carried out among the Asmat population of Irian Jaya (Indonesian New Guinea). 158 serum samples were examined: besides the HAV-IgC marker, total-HBV and HBsAg, anti-HBs, anti-HBc were investigated. 98.7% of total sample were found positive to HAV and 83.3% were positive to at least one HBV serum marker of infection. The results are analyzed according to sex, age and locality of residence. Males show a higher positivity to HBV, but the difference is not statistically significant. The highest infection rate is present in the young age group (11–20 years), this phenomenon being and index of high endemicity. In the subjects belonging to a missionary school community, positivity and prevalence of infection are high and equally distributed in both sexes, while in the village sample males show a higher infection rate. The tropical environment, the nutritional imbalances and the village hygienic conditions are considered responsible for the spread of HAV infection. Since HBV affects our population precociously, the family and especially the mother can be regarded as the first vehicle of infection transmission. Among the possible causes of HBV diffusion outside the family, the custom of ear and nose piercing as well as the use of recently introduced items are taken into account. Traditional and ritual heterosexual as well as homosexual behaviours are then considered among the possible causes of infection diffusion. Finally, the reasons why HAV and HBV affect the population under an asymptomatic or an unrecognised form are suggested.     

Synthesis and biological evaluation of nucleoside analogues than contain silatrane on the basis of the structure of acyclovir (ACV) as novel inhibitors of hepatitis B virus (HBV)

Hepatitis B virus (HBV) infection causes major public health problems worldwide. Acyclovir (ACV) is mainly used to inhibit herpes simplex virus (HSV) rather than HBV. In this study, we used the combination principle to design and synthesize nucleoside analogues that contain silatrane on the basis of the structure of ACV. We found that the compounds were effective inhibitors of HBV, both in vitro and in vivo. All of the compounds showed suppressive activity on the expression of HBV surface antigen (HBsAg) and HBV e antigen (HBeAg) in the HepG2.2.15 cell line with low cytotoxicity. One of compounds was studied in HBV transgenic mice model, and the test results showed its ability to reduce the levels of HBsAg, HBeAg and HBV DNA by ELASE and qPCR. Furthermore, significant improvement of T lymphocyte was observed after treatment, as evaluated by flow cytometry (FCM).     

Novel,Potentially Zoonotic Paramyxoviruses from the African Straw-Colored Fruit Bat Eidolon helvum

Bats carry a variety of paramyxoviruses that impact human and domestic animal health when spillover occurs. Recent studies have shown a great diversity of paramyxoviruses in an urban-roosting population of straw-colored fruit bats in Ghana. Here, we investigate this further through virus isolation and describe two novel rubulaviruses: Achimota virus 1 (AchPV1) and Achimota virus 2 (AchPV2). The viruses form a phylogenetic cluster with each other and other bat-derived rubulaviruses, such as Tuhoko viruses, Menangle virus, and Tioman virus. We developed AchPV1- and AchPV2-specific serological assays and found evidence of infection with both viruses in Eidolon helvum across sub-Saharan Africa and on islands in the Gulf of Guinea. Longitudinal sampling of E. helvum indicates virus persistence within fruit bat populations and suggests spread of AchPVs via horizontal transmission. We also detected possible serological evidence of human infection with AchPV2 in Ghana and Tanzania. It is likely that clinically significant zoonotic spillover of chiropteran paramyxoviruses could be missed throughout much of Africa where health surveillance and diagnostics are poor and comorbidities, such as infection with HIV or Plasmodium sp., are common.     

The epidemiology of human immunodeficiency virus in South Africa

We review the epidemiology of human immunodeficiency virus (HIV) in South Africa where the prevalence of HIV infection is among the highest in the world. The epidemic reached South Africa relatively recently but the prevalence of infection has increased rapidly and there are significant differences among provinces. Although few 15-year-old people are infected the prevalence increases rapidly with age thereafter, especially among women. The prevalence of herpes simplex virus type 2 exceeds that of HIV and curable sexually transmitted infections are common. 'Circular migration' may help to explain the high rates and rapid spread of HIV in the region. The incidence of tuberculosis has increased dramatically as a result of the HIV epidemic. Antiretroviral therapy for the prevention of vertical transmission has been shown to be effective in local conditions but transmission through breast-feeding remains problematical. While some epidemiological models have been developed, much more needs to be done in this regard in order to plan, coordinate and evaluate an effective response to the epidemic. We conclude by discussing some of the research that is needed and steps that could be taken to reduce the continued spread of the infection.     

Mechanisms and Effects on HBV Replication of the Interaction between HBV Core Protein and Cellular Filamin B

Hepatitis B virus (HBV) infection is one of the major problems that threatens global health. There have been many studies on HBV, but the relationship between HBV and host factors is largely unexplored and more studies are needed to clarify these interactions. Filamin B is an actin-binding protein that acts as a cytoskeleton protein, and it is involved in cell development and several signaling pathways. In this study, we showed that filamin B interacted with HBV core protein, and the interaction promoted HBV replication. The interaction between filamin B and core protein was observed in HEK 293T, Huh7 and HepG2 cell lines by co-immunoprecipitation and co-localization immnofluoresence. Overexpression of filamin B increased the levels of HBV total RNAs and pre-genome RNA (pgRNA), and improved the secretion level of hepatitis B surface antigen (HBsAg) and hepatitis B e antigen (HBeAg). In contrast, filamin B knockdown inhibited HBV replication, decreased the level of HBV total RNAs and pgRNA, and reduced the secretion level of HBsAg and HBeAg. In addition, we found that filamin B and core protein may interact with each other via four blocks of argentine residues at the C-terminus of core protein. In conclusion, we identify filamin B as a novel host factor that can interact with core protein to promote HBV replication in hepatocytes. Our study provides new insights into the relationship between HBV and host factors and may provide new strategies for the treatment of HBV infection.     

Prevalence of human immunodeficiency virus infection in alcoholics

To verify the prevalence of infection by human immunodeficiency virus (HIV) in alcoholics we studied 131 alcoholic patients (119 males and 12 females) with a mean age of 44.3 +/- 10.8 years. Serum samples were collected from this group and analysed, by ELISA, for antibodies against HIV as well as for serological markers for hepatitis B virus (HBV) and hepatitis C virus (HCV). As we have previously described, we found a high prevalence of HBV (26.4%) and HCV (4.2%) markers as compared to the prevalence of these markers in samples of normal blood donors from Uberlandia's Hemocentro Regional, which are 4% and 0.4%, respectively. Of the 131 patients, four (3%) had antibodies against HIV, three (75%) of which were injecting drug users (IDU). In the HIV-negative group, only one patient was an IDU. The prevalence of HIV in our population, according to data from the city's Health Secretary, varies from 3.1% to 6.2%. We conclude that, at least for the moment, alcoholism per se, did not constitute an important risk factor for HIV infection. However, acquired immunodeficiency syndrome is a rather recent disease as compared to hepatitis B and C and, as the transmission routes are similar for HIV and hepatitis viruses, an increase in the incidence of HIV infection in alcoholics may be just a question of time.     

Seroepidemiology of viral infections among intravenous drug users in northern California.

Intravenous drug users are frequently exposed to parenterally transmitted viral infections, and these infections can spread to the general population through sexual activity. We investigated the prevalence of serologic markers for human immunodeficiency virus type 1 (HIV-1), human T-cell lymphotropic virus type I/II (HTLV-I/II), hepatitis B virus (HBV), and hepatitis C virus (HCV) in intravenous drug users and their sexual contacts. Of 585 drug users from northern California tested for these serologic markers, 72% were reactive for the antibody to HCV, 71% for the antibody to hepatitis B core antigen, 12% for HTLV-I/II antibodies, and 1% for the HIV-1 antibody. The prevalence of serologic markers for these four viruses correlated with the duration of intravenous drug use, the ethnic group, and the drug of choice. More than 85% of subjects infected with either HCV or HBV were coinfected with the other virus. All persons reactive to HTLV-I/II antibodies had antibodies for either HBV or HCV. Of 81 sexual contacts tested, 17% had evidence of HBV infection while only 6% were reactive for HTLV-I/II antibodies and 4% for the antibody to HCV. None of this group was infected with HIV-1. We conclude that HTLV-I/II and HCV are inefficiently transmitted to sexual contacts while HBV is spread more readily. Programs designed to discourage the sharing of drug paraphernalia, such as needle and syringe exchanges, should decrease the risk of parenterally spread viral infections in intravenous drug users and thus slow the spread of these infections to the general population.     

Herpes Simplex Virus 1 Targets the Murine Olfactory Neuroepithelium for Host Entry

Herpes simplex virus 1 (HSV-1) is a ubiquitous and important human pathogen. It is known to persist in trigeminal ganglia (TG), but how it reaches this site has been difficult to determine, as viral transmission is sporadic, pathogenesis is complicated, and early infection is largely asymptomatic. We used mice to compare the most likely natural HSV-1 host entry routes: oral and nasal. Intranasal infection was 100-fold more efficient than oral and targeted predominantly the olfactory neuroepithelium. Live imaging of HSV-1-expressed luciferase showed infection progressing from the nose to the TG and then reemerging in the facial skin. The brain remained largely luciferase negative throughout. Infected cell tagging by viral Cre recombinase expression in floxed reporter gene mice showed nasal virus routinely reaching the TG and only rarely reaching the olfactory bulbs. Thus, HSV-1 spread from the olfactory neuroepithelium to the TG and reemerged peripherally without causing significant neurological disease. This recapitulation of typical clinical infection suggests that HSV-1 might sometimes also enter humans via the respiratory tract.