Novel insights into viral infection and oncogenesis from Koala Retrovirus (KoRV) infection of HEK293T cells

Koala retrovirus is thought to be an underlying cause of high levels of neoplasia and immunosuppression in koalas. While epidemiology studies suggest a strong link between KoRV and disease it has been difficult to prove causality because of the complex nature of the virus, which exists in both endogenous and exogenous forms. It has been difficult to identify koalas completely free of KoRV, and infection studies in koalas or koala cells are fraught with ethical and technical difficulties, respectively. This study uses KoRV infection of the susceptible human cell line HEK293T and RNAseq to demonstrate gene networks differentially regulated upon KoRV infection. Many of the pathways identified are those associated with viral infection, such as cytokine receptor interactions and interferon signalling pathways, as well as viral oncogenesis pathways. This study provides strong evidence that KoRV does indeed behave similarly to infectious retroviruses in stimulating antiviral and oncogenic cellular responses. In addition, it provides novel insights into KoRV oncogenesis with the identification of a group of histone family genes that are part of several oncogenic pathways as upregulated in KoRV infection

Koala retrovirus viral load and disease burden in distinct northern and southern koala populations

Koala retrovirus (KoRV) displays features of both an endogenous and exogenous virus and is linked to neoplasia and immunosuppression in koalas. This study explores the apparent differences in the nature and impact of KoRV infection between geographically and genetically separated "northern" and "southern" koala populations, by investigating the disease status, completeness of the KoRV genome and the proviral (DNA) and viral (RNA) loads of 71 northern and 97 southern koalas. All northern animals were positive for all KoRV genes (gag, pro-pol and env) in both DNA and RNA forms, whereas many southern animals were missing one or more KoRV genes. There was a significant relationship between the completeness of the KoRV genome and clinical status in this population. The proviral and viral loads of the northern population were significantly higher than those of the southern population (P

Genetic diversity of Koala retrovirus (KoRV) env gene subtypes: Insights into northern and southern koala populations

Koala retrovirus (KoRV) is a recently endogenised retrovirus associated with neoplasia and immunosuppression in koala populations. The virus is known to display sequence variability and to be present at varying prevalence in different populations, with animals in southern Australia displaying lower prevalence and viral loads than northern animals. This study used a PCR and next generation sequencing strategy to examine the diversity of the KoRV env gene in both proviral DNA and viral RNA forms in two distinct populations representative of the “northern” and “southern” koala genotypes. The current study demonstrated that the full range of KoRV subtypes is present across both populations, and in both healthy and sick animals. KoRV-A was the predominant proviral subtype in both populations, but there was marked diversity of DNA and RNA subtypes within individuals. Many of the northern animals displayed a higher RNA viral diversity than evident in their proviral DNA, indicating relatively higher replication efficiency of non-KoRV-A subtypes. The southern animals displayed a lower absolute copy number of KoRV than the northern animals as reported previously and a higher preponderance of KoRV-A in individual animals. These discrepancies in viral replication and diversity remain unexplained but may indicate relative protection of the southern population from KoRV replication due to either viral or host factors and may represent an important protective effect for the host in KoRV’s ongoing entry into the koala genome

Understanding individual, family and community perspectives on delaying early birth among adolescent girls

Background: Pregnancy among adolescent girls in Bangladesh is high, with 66% of women under the age of 18 reporting a first birth; this issue is particularly acute in the northern region of Bangladesh, an area that is especially impoverished and where girls are at heightened risk. Using formative research, CARE USA examined the underlying social, individual and structural factors influencing married girls’ early first birth and participation in alternative opportunities (such as education or economic pursuits) in Bangladesh. Methods: In July of 2017, researchers conducted in-depth interviews of community members in two sub-districts of northern Bangladesh (Kurigram Sadar and Rajarhat). Participants (n = 127) included adolescent girls (both married and unmarredi), husbands of adolescent girls, influential adults in the girls’ lives, community leaders, and health providers. All interviews were transcribed, coded and organized using Dedoose software. Results: Participants recognize the health benefits of delaying first birth, but stigma around infertility and contraceptive use, pressure from mothers-in-law and health provider bias interfere with a girl’s ability to delay childbearing. Girls’ social isolation, lack of mobility or autonomy, and inability to envision alternatives to early motherhood compound the issue; provider bias may also prevent access to methods. While participants agree that pursuit of education and economic opportunities are important, better futures for girls do not necessarily supersede their marital obligations of childrearing and domestic chores. Conclusions: Findings indicate the need for a multi-level approach to delaying early birth and stimulating girls’ participation in economic and educational pursuits. Interventions must mitigate barriers to reproductive health care; train adolescent girls on viable economic activities; and provide educational opportunities for girls. Effective programs should also address contextual issues by including immediate members of the girls’ families, particularly the husband and mother-in-law