TWiM 64: URI and UTI at ICAAC

This episode of TWiM was recorded at the 53rd ICAAC in Denver, Colorado, where Michael Schmidt and I spoke with James Gern about rhinoviruses, and James Johnson about extra-intestinal pathogenic E. coli.

You can find TWiM #64 at microbeworld.org, or view the video below.

XMRV in human respiratory tract

An important question about the retrovirus XMRV, which has been implicated in prostate cancer and chronic fatigue syndrome, is where the virus replicates in humans. Such information would provide clues about how infection might be transmitted. To date the virus has been detected in malignant prostate cells and in the peripheral blood mononuclear cells and plasma of patients with CFS. A new study reveals that XMRV is present in respiratory secretions.

Polymerase chain reaction was used to detect XMRV in 267 respiratory samples taken from German patients. One group comprised sputum and nasal swab specimens from 75 travelers from Asia who had respiratory tract infections. The second group consisted of 31 bronchoalveolar lavage samples from patients with chronic obstructive pulmonary disease, while samples from the third group were from 161 immunosuppressed patients with severe respiratory tract infections. The study included 62 healthy controls. It should be noted that none of the patients had been diagnosed with CFS.

XMRV sequences were detected in 3 of 75 samples (2.3%) in group 1, 1 of 31 samples (3.2%) in group 2, and 16/161 (9.9%) in group 3. Six of the XMRV-positive samples in the second group also contained rhinovirus, adenovirus, or pathogenic fungi. The higher rate of detection of XMRV and other microbes in immunosuppressed individuals is not unexpected. The control group contained 2 of 62 samples (3.2%) positive for XMRV.

The presence of XMRV in PBMCs and plasma suggests a blood-borne route of transmission of the virus: transfusions, health care associated needle sticks, and intravenous drug use. Does finding XMRV in the respiratory tract prove that the virus can be transmitted by the respiratory route? No, not until we have other information, including the level of virus in respiratory secretions, and the infectivity of XMRV. In this context it is interesting to note that it was not possible to isolate infectious XMRV from the respiratory tract of the German patients.

Reviewing the transmission of another human retrovirus, HIV-1, is instructive in understanding the pathogenesis of XMRV infection. The main modes of transmission of HIV-1 are sexual, parenteral, and from mother to infant. These routes of transmission are consistent with levels of infectious virus in body fluids (shown in this table). Viral RNA can be detected at several levels of the respiratory tract, but respiratory secretions rarely transmit HIV.

FIsher, N., Schulz, C., Stieler, K., Hohn, O., Lange, C., Drosten, C., & Aepfelbacher, M. (2010). Xenotropic murine leukemia virus-related gammaretrovirus in respiratory tract Emerg. Inf. Dis. : 10.3201/eid1606.100066

Viruses and the respiratory tract

Now that we have a rudimentary understanding of influenza virus replication, we can begin to consider how the virus causes disease – a field of study called viral pathogenesis. The first step in this process is virus entry into the body.

virus-entryThe human body is covered with skin, which has a dead outer layer that cannot support viral replication and also serves as a impermeable barrier. Viruses may breach the skin via a vector bite, needle injury, animal bite, or abrasion. However, layers of exposed living cells must be present to absorb food, exchange gases, and release urine and other fluids. These mucosal layers serve as easy sites of entry for viruses.

The respiratory tract is the most common route of viral entry, a consequence of the exposed mucosal surface and the resting ventilation rate of 6 liters of air per minute. The huge absorptive area of the human lung (140 square meters) also plays a role. Large numbers of foreign particles and aerosolized droplets – often containing virions – are introduced into the respiratory tract each minute. The reason why we are not more frequently infected is that there are numerous defense mechanisms to protect the respiratory tract. Mechanical barriers abound – for example, the tract is lined with a mucociliary blanket comprising ciliated cells, mucus-secreting goblet cells, and subepithelial mucus-secreting glands. Foreign particles that enter the nasal cavity or upper respiratory tract are trapped in mucus and carried to the back of the throat, where they are swallowed. If particles reach the lower respiratory tract, they may also be trapped in mucus, which is then brought up and out of the lungs by ciliary action. The lowest reaches of the respiratory tract – the aveoli – are devoid of cilia. However, these gas-exchanging sacs are endowed with macrophages, whose job it is to ingest and destroy particles.

respiratory-tract1

As we discussed previously, viruses may enter the respiratory tract in aerosolized droplets produced by coughing, sneezing, or simply talking, singing, or breathing. Infection may also be spread by contact with saliva or other respiratory secretions from an infected individual. The larger aerosol droplets land in the nose, while smaller ones may venture deeper into the respiratory tract, even as far as the aveoli.

For a virus to successfully establish an infection in the respiratory tract, it must avoid being swept away by mucus or engulfed by alveolar macrophages. Then there are the more specific immune mechanisms that may intervene – a topic we’ll consider later. Suffice it to say that if a virus establishes an infection in the respiratory tract, it has surmounted a number of formidable barriers which ensure that we are not continuously infected.