Introduction and Discussion
Stealth adaptation refers to a viral immune evasion mechanism resulting
from the deletion or mutation of the viral genes coding for the
relatively few components, that are normally targeted by the cellular
immune system [1-7]. It was initially described in a cytopathic
virus cultured from a patient with chronic fatigue syndrome (CFS)
[2]. Sequence analyses of this prototypic stealth adapted virus
indicate the further acquisition of genetic sequences from cellular and
bacterial genomes [8-15]. These additional sequences are seemingly
abandoning their host in favor of further passage together with the
remaining sequences of the originating virus. As such, they are referred
to as renegade sequences [10-15]. Although the prototypic stealth
adapted virus originated from an African green monkey simian
cytomegalovirus (SCMV), the identified cellular-derived renegade
sequences are from the human genome rather than from an African green
monkey genome [10]. The likely explanation is that the African green
monkey cellular sequences have been replaced by homologous recombination
with corresponding human sequences. This conclusion is supported by
sequencing data from the polymerase chain reaction (PCR) products
generated from certain other stealth adapted viruses cultured from CFS
patients. Of the five cultures from which PCR products were sequenced,
three have cellular sequences derived from the rhesus monkey genome. In
one of the cultures, four of the seven sequenced PCR products are rhesus
in origin and the other three are of human origin [13-14]. Moreover,
the human sequences have counterpart sequences in the rhesus genome
[13-14].
Examples of the human-genome matching sequence from stealth virus-1 and
a rhesus-genome matching sequence from stealth virus-3 are provided in
Tables 1 and 2, respectively. Both sequences were generated using the
same set of primers in the PCR. The primer sequences were excluded from
the genetic analyses.
Cultured kidney cells from cytomegalovirus-infected rhesus and
cynomolgus monkeys were used before the switch to African green monkeys
in the production of poliovirus vaccines [16-21]. SCMV DNA is
present in almost half of tested earlier polio vaccine lots produced
from African green monkeys, while rhesus cytomegalovirus DNA is present
in most vaccines produced in the cultured kidney cells of rhesus and
cynomolgus monkeys [19-20].
Based on using various primers in the PCR, several of the partially
analyzed cultured stealth adapted viruses are also derived from SCMV
[3, 5]. Certain stealth adapted viruses have more likely arisen from
human herpes simplex virus (HSV), Epstein Barr virus, and human
adenovirus. There are also data supporting a possible HIV-derived
stealth adapted virus. Based on research from others, enteroviruses may
contribute to the formation of stealth adapted viruses, possibly even
poliovirus. Thus, stealth adaptation is viewed as a generic process
applicable to all viruses.
There are major implications regarding the sharing of cellular sequences
between stealth viruses cultured from three unrelated individuals
[13-14]. Rather than being a frequent and essentially random
incorporation of renegade cellular sequences, this may be a relatively
rare occurrence. Indeed, the incorporated sequence could possibly be
involved in the virus regaining infectivity. To date, the incorporated
cellular sequences are non-coding and positioned either within or
between transcribed genes [10, 13]. In contrast, the incorporated
bacterial renegade sequences correspond to at least parts of
protein-coding genes [9-11, 13-14]. Various long non-coding RNA
(LncRNA) cellular sequences are associated with the pathogenesis of
specific illnesses [22-28]. This raises the possibility of certain
stealth adapted viruses inducing specific illnesses attributed to their
incorporated cellular sequences. While these could include known genetic
diseases, they could manifest as entirely new disease entities.
Minor sequence variability is present between specific cell-derived
renegade sequences in different individuals and even between the same
originating cellular sequence in the virus cultured from the same
individual. The variability results from nucleotide additions,
deletions, or substitutions. The degree of sequence variability along
with other data is consistent with RNA to DNA reverse transcription
[29]. Generic instability of the cellular sequences could also
change the pathogenicity of the virus. Identifying increased levels of a
cellular sequence in pathological tissues, for example, a particular
LncRNA sequence, is normally assumed to reflect an intrinsic genetic
mutation. It could, however, reflect an infectious process.
It is of utmost importance to culture, isolate, and sequence stealth
adapted viruses from human and animal populations. The culturing of
stealth adapted viruses was deemed to be putting the Nation’s health in
“Immediate Jeopardy” [7]. This was undoubtedly due to the linking
of these viruses to the inadvertent use of cytomegalovirus-infected
monkeys in the production of polio vaccines [3, 16-20]. The
determination was also precipitated by the positive cultures obtained
from some individuals donating blood to a transfusion center. Prior to
prohibiting further clinical testing, stealth adapted viruses were
routinely being cultured from CFS patients, children with autism, adults
with severe psychiatric illnesses, patients diagnosed as having chronic
Lyme disease, and with other illnesses, including multiple myeloma
[29-36]. Patient support groups do not wish to be burdened with the
added concern of being potentially infectious to others. They do,
however, pose occupational risks to others. There are also the risks of
two-way virus transmissions between humans and animals.
Tentative evidence for virus transmission between individuals is
provided by illnesses occurring within families [36]. A prime
example is the occurrence of autism in children born to mothers with a
prior or current history of CFS. Diverse manifestations of the illnesses
among family members, such as those described in an earlier publication
[36], could reflect minor changes in the infecting virus or
preexisting disease susceptibility in the cross-infected family member.
Some examples of caregiver burnout may also be attributed to acquired
infections [36]. Occupational exposure to stealth adapted viruses is
also to be expected, especially among human and animal healthcare
providers, prison guards, schoolteachers, and other groupings of working
individuals, such as orchestra players [29-40]. Disability tends to
be more common among these groups, as unfortunately is suicide. Although
numerous community outbreaks of CFS have been reported, Public Health
officials have downplayed the likelihood of infection in favor of a
hysterical reaction of wanting to be sick. This issue can most easily be
settled by performing adequate virus cultures, sequencing of the
viruses, and undertaking animal transmission studies. Public Health
officials have been slow to respond to the published data on the first
stealth adapted virus to be cultured from a CFS patient [2]. The
second cultured virus was from a patient who was initially diagnosed
with schizophrenia, but the diagnosis was later changed to bipolar
psychosis [33]. Patients with mental illnesses deserve to know if a
stealth adapted virus infection is contributing to their illness. As
will be discussed in a subsequent article, means are available to
suppress stealth adapted and indeed all viruses via the alternative
cellular energy (ACE) pathway [41-43].