• endogenous retroviruses
• koala retrovirus
• neutralization
• tolerance
• vaccination

• Chlamydia
• Immune system
• Koala
• Koala retrovirus

• Animals
• Australia
• Bacterial Vaccines/immunology
• Chlamydia/physiology
• Chlamydia Infections/immunology
• Communicable Diseases/immunology
• Host-Pathogen Interactions
• Humans
• Immunity/genetics
• Immunosuppression Therapy
• Phascolarctidae/immunology
• Retroviridae/physiology
• Retroviridae Infections/immunology
• Urogenital System/immunology
• Urogenital System/microbiology
• Urogenital System/virology

The virulence of chlamydial infection in wild koalas is highly variable between individuals. Some koalas can be infected (PCR positive) with Chlamydia for long periods but remain asymptomatic, whereas others develop clinical disease. Chlamydia in the koala has traditionally been studied without regard to coinfection with other pathogens, although koalas are usually subject to infection with koala retrovirus (KoRV). Retroviruses can be immunosuppressive, and there is evidence of an immunosuppressive effect of KoRV in vitro. Originally thought to be a single endogenous strain, a new, potentially more virulent exogenous variant (KoRV-B) was recently reported. We hypothesized that KoRV-B might significantly alter chlamydial disease outcomes in koalas, presumably via immunosuppression. By studying sub-groups of Chlamydia and KoRV infected koalas in the wild, we found that neither total KoRV load (either viraemia or proviral copies per genome), nor chlamydial infection level or strain type, was significantly associated with chlamydial disease risk. However, PCR positivity with KoRV-B was significantly associated with chlamydial disease in koalas (p = 0.02961). This represents an example of a recently evolved virus variant that may be predisposing its host (the koala) to overt clinical disease when co-infected with an otherwise asymptomatic bacterial pathogen (Chlamydia).

• Endogenous retroviruses
• Koala
• PCR
• Retroviruses

• Adult
• Base Sequence
• Brain/pathology
• Chlamydia Infections/microbiology
• Chlamydophila pneumoniae/genetics
• DNA, Bacterial/cerebrospinal fluid
• DNA, Bacterial/genetics
• Female
• Humans
• Magnetic Resonance Imaging
• Male
• Middle Aged
• Molecular Sequence Data
• Multiple Sclerosis, Relapsing-Remitting/diagnosis
• Multiple Sclerosis, Relapsing-Remitting/microbiology
• Retrospective Studies

Multiple Sclerosis (MS) is the most common demyelinating disease of man with over 400,000 cases in the United States and over 2.5 million cases worldwide. There are over 64,000 citations in Pubmed dating back as far as 1887. Much has been learned over the past 129 years with a recent burst in therapeutic options (mostly anti-inflammatory) with newer medications in development that are neuroprotective and/or neuroreparative. However, with all these advancements the cause of MS remains elusive. There is a clear interplay of genetic, immunologic, and environmental factors that influences both the development and progression of this disorder. This chapter will give a brief overview of the history and pathogenesis of MS with attention to how host immune responses in genetically susceptible individuals contribute to the MS disease process. In addition, we will explore the role of infectious agents in MS as potential “triggers” of disease. Models of virus-induced demyelination will be discussed, with an emphasis on the recent interest in human herpesviruses and the role they may play in MS disease pathogenesis. Although we remain circumspect as to the role of any microbial pathogen in MS, we suggest that only through well-controlled serological, cellular immune, molecular, and animal studies we will be able to identify candidate agents. Ultimately, clinical interventional trials that either target a specific pathogen or class of pathogens will be required to make definitive links between the suspected agent and MS.

Koala retroviruses (KoRV) have been isolated from wild and captive koalas in Australia as well as from koala populations held in zoos in other countries. They are members of the genus Gammaretrovirus, are most closely related to gibbon ape leukemia virus (GaLV), feline leukemia virus (FeLV) and porcine endogenous retrovirus (PERV) and are likely the result of a relatively recent trans-species transmission from rodents or bats. The first KoRV to be isolated, KoRV-A, is widely distributed in the koala population in both integrated endogenous and infectious exogenous forms with evidence from museum specimens older than 150 years, indicating a relatively long engagement with the koala population. More recently, additional subtypes of KoRV that are not endogenized have been identified based on sequence differences and host cell receptor specificity (KoRV-B and KoRV-J). A specific association with fatal lymphoma and leukemia has been recently suggested for KoRV-B. In addition, it has been proposed that the high viral loads found in many animals may lead to immunomodulation resulting in a higher incidence of diseases such as chlamydiosis. Although the molecular basis of this immunomodulation is still unclear, purified KoRV particles and a peptide corresponding to a highly conserved domain in the envelope protein have been shown to modulate cytokine expression in vitro, similar to that induced by other gammaretroviruses. While much is still to be learned, KoRV induced lymphoma/leukemia and opportunistic disease arising as a consequence of immunomodulation are likely to play an important role in the stability of koala populations both in the wild and in captivity.

Chlamydophila pneumoniae (C. pneumoniae) is an obligate, intracellular bacterium associated with a wide variety of acute and chronic diseases. C. pneumoniae infection is characterized by persistence and immunopathological damage to host target tissues, including the lung. Over the past 20 years, a variety of studies have investigated a possible link between C. pneumoniae infection and atherosclerosis, because of its role in all stages of atherosclerosis, from initial inflammatory lesions to plaque rupture. In the current highly active antiretroviral therapy (HAART) era, many human immunodeficiency virus (HIV)-infected patients are experiencing health problems that accompany the aging process, mainly the risk of cardiovascular disease (CVD). There is renewed interest in a link between atherosclerotic CVD and as yet poorly defined environmental exposures, including infectious agents. On the one hand, the patient with HIV and lipodystrophy caused by HAART and exacerbated by C. pneumoniae infection could be a factor of risk for atherosclerosis. An assessment of the therapy against C. pneumoniae and HAART should always be conducted. It is advisable that HIV-acquired immune deficiency syndrome patients undergo a serological test to determine exposure to C. pneumoniae and to assess treatment options. On the other hand, in patients with a positive serology to C. pneumoniae, an increment of the body mass index has been found; therefore, it is probable that the recurrent infection may play an important role in creating adverse endothelial conditions allowing the infection by C. pneumoniae in its chronic form, to damage the endothelial surface. Vascular studies would be necessary for corroboration.

• Acquired immune deficiency syndrome
• Atheroma
• Chlamydophila pneumoniae
• Immunobiology of infection
• Obesity
• Inflammation

Chlamydophila pneumoniae is an intracellular pathogen responsible for a number of different acute and chronic infections. The recent deepening of knowledge on the biology and the use of increasingly more sensitive and specific molecular techniques has allowed demonstration of C. pneumoniae in a large number of persons suffering from different diseases including cardiovascular (atherosclerosis and stroke) and central nervous system (CNS) disorders. Despite this, many important issues remain unanswered with regard to the role that C. pneumoniae may play in initiating atheroma or in the progression of the disease. A growing body of evidence concerns the involvement of this pathogen in chronic neurological disorders and particularly in Alzheimer's disease (AD) and Multiple Sclerosis (MS). Monocytes may traffic C. pneumoniae across the blood-brain-barrier, shed the organism in the CNS and induce neuroinflammation. The demonstration of C. pneumoniae by histopathological, molecular and culture techniques in the late-onset AD dementia has suggested a relationship between CNS infection with C. pneumoniae and the AD neuropathogenesis. In particular subsets of MS patients, C. pneumoniae could induce a chronic persistent brain infection acting as a cofactor in the development of the disease. The role of Chlamydia in the pathogenesis of mental or neurobehavioral disorders including schizophrenia and autism is uncertain and fragmentary and will require further confirmation.

• Animals
• Cell Line
• Disease Transmission, Infectious
• Endogenous Retroviruses/classification
• Endogenous Retroviruses/genetics
• Endogenous Retroviruses/pathogenicity
• Gammaretrovirus/classification
• Gammaretrovirus/genetics
• Gammaretrovirus/pathogenicity
• Humans
• Molecular Sequence Data
• Phascolarctidae
• Rats
• Retroviridae Infections/transmission
• Retroviridae Infections/veterinary
• Retroviridae Infections/virology

• Animals
• Endogenous Retroviruses/classification
• Endogenous Retroviruses/enzymology
• Endogenous Retroviruses/genetics
• Neoplasms/epidemiology
• Neoplasms/virology
• Phascolarctidae/virology
• RNA, Viral/blood
• RNA, Viral/genetics
• Reverse Transcriptase Polymerase Chain Reaction/methods
• Viremia

• Adult
• Antibody Formation/immunology
• Brain/diagnostic imaging
• Brain/immunology
• Brain/microbiology
• Chlamydia Infections/cerebrospinal fluid
• Chlamydia Infections/complications
• Chlamydia Infections/immunology
• Chlamydophila pneumoniae/immunology
• Chlamydophila pneumoniae/pathogenicity
• Encephalitis/cerebrospinal fluid
• Encephalitis/immunology
• Female
• Humans
• Immunoglobulin G/blood
• Immunoglobulin G/cerebrospinal fluid
• Male
• Middle Aged
• Multiple Sclerosis/cerebrospinal fluid
• Multiple Sclerosis/immunology
• Multiple Sclerosis/microbiology
• Radiography